Today's Issue

Main Topic: Three biotech startups with real technology, clinical progress, and investment potential

Subtitles:

• Verve Therapeutics: editing cholesterol genes with one injection

• Fauna Bio: using hibernating animals to create human therapeutics

• Altos Labs: the billionaire-backed cellular rejuvenation company

Abstract: Three biotech startups represent high-risk, high-reward investment opportunities in 2025: Verve Therapeutics (NASDAQ: VERV) is developing in vivo base editing for cardiovascular disease, with Phase 1b trial data showing permanent LDL reduction through single-dose gene editing; Fauna Bio uses comparative genomics of hibernating and long-lived animals to discover drug targets for metabolic and age-related diseases, with preclinical compounds in development; and Altos Labs, backed by $3 billion from Jeff Bezos and Yuri Milner, is pursuing cellular reprogramming to reverse aging at the cellular level with an all-star scientific team. This newsletter examines each company's technology, clinical/preclinical progress, market potential, and investment considerations including risks.Introduction

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1. Verve Therapeutics: Editing Cholesterol Genes With One Injection 💉🧬

The Technology: Verve uses in vivo base editing (a precise form of gene editing that changes single DNA letters in living patients without cutting the DNA double helix) to permanently lower cholesterol by targeting the PCSK9 gene in the liver.

Why it matters: Cardiovascular disease kills more people globally than any other cause. Statins work but require daily pills with compliance issues and side effects. PCSK9 inhibitors (injectable drugs like Repatha) are extremely effective but cost $6,000+ annually and require frequent injections. Verve's approach: one injection, permanent cholesterol reduction.

Clinical progress: Phase 1b trial data released in 2024 showed successful gene editing in humans with measurable PCSK9 reduction and corresponding LDL lowering. One patient achieved 55% reduction in LDL cholesterol that persisted for months after a single dose. This proof-of-concept validates the technology in humans, not just animals.

Market potential: The cardiovascular disease drug market exceeds $150 billion annually. If Verve can deliver permanent cholesterol control with one injection priced at $50,000-100,000, the lifetime cost compares favorably to decades of PCSK9 inhibitors while eliminating compliance issues. Potential addressable market: tens of millions of patients with familial hypercholesterolemia or statin-intolerant high cholesterol.

Investment case: Publicly traded (NASDAQ: VERV), currently valued around $1-2 billion market cap. The company has partnerships with Eli Lilly and strong IP. Phase 2 trials are ongoing, with pivotal trials expected by 2026-2027.

Risks: Gene editing safety concerns (off-target effects, immune responses), regulatory hurdles (FDA has never approved in vivo gene editing for non-fatal conditions), competition from other gene editing companies and traditional pharmaceuticals, and the technology could fail in larger trials.

2. Fauna Bio: Using Hibernating Animals to Create Human Therapeutics 🐻💊

The Technology: Fauna Bio uses comparative genomics of animals with extraordinary metabolic abilities (bears that hibernate without muscle loss, bats that live 10x longer than expected, whales resistant to cancer) to discover drug targets for human diseases.

The insight: Evolution has already solved problems medicine struggles with. Bears survive months without eating, moving, or urinating during hibernation yet don't develop muscle atrophy, osteoporosis, or kidney failure that would kill humans in weeks.

If we can identify the genes and pathways enabling this, we can develop drugs replicating those protective effects.

The approach: Fauna sequences genomes of hibernators and other exceptional animals, identifies genes differentially expressed during hibernation or longevity, validates these targets in human cells and mouse models, then develops small molecule drugs hitting those targets.

Pipeline progress: Fauna has multiple preclinical programs targeting metabolic health, muscle preservation, and age-related diseases. The company announced collaborations with major pharma (including Eli Lilly) to develop drugs from their discoveries. While no clinical trials yet, the preclinical data is compelling.

Market potential: Metabolic diseases (diabetes, obesity, metabolic syndrome) affect billions globally. Muscle wasting affects cancer patients, elderly, and bedridden individuals. The addressable markets are enormous if the drugs work.

Investment case: Private company that raised $11M in Series A (2023) and recently completed Series B funding. Not publicly tradeable yet but worth watching for IPO or acquisition. The founding team includes Stanford and UC Berkeley scientists with strong evolutionary biology and drug development credentials.

Risks: Early stage (no clinical data yet), drug development failure rates are 90%+, evolutionary solutions may not translate to humans despite genetic conservation, and funding could dry up if preclinical results disappoint.

3. Altos Labs: The Billionaire-Backed Cellular Rejuvenation Company 🧬⏳

The Technology: Altos is pursuing cellular reprogramming to reverse biological aging by resetting cells to younger states using Yamanaka factors (transcription factors that can revert adult cells to embryonic-like stem cells).

The science: In 2006, Shinya Yamanaka discovered that four transcription factors (Oct4, Sox2, Klf4, c-Myc) can reprogram adult cells into induced pluripotent stem cells (iPSCs), essentially resetting their biological age. The discovery won the Nobel Prize. The problem: fully reprogrammed cells become stem cells, losing their original identity. Altos is working on partial reprogramming, using transient exposure to Yamanaka factors to rejuvenate cells without losing their function.

The company: Founded in 2021 with $3 billion in funding from Jeff Bezos, Yuri Milner, and other billionaires. The team includes Nobel laureates, top aging researchers (including Juan Carlos Izpisua Belmonte, Steve Horvath), and drug development veterans. Multiple research hubs in US and UK.

What they're developing: Altos is targeting age-related diseases initially rather than "curing aging" outright. Potential early targets include macular degeneration, osteoarthritis, fibrosis, and neurodegenerative diseases. The approach could involve cell therapies (delivering rejuvenated cells) or drugs that trigger partial reprogramming.

Timeline: Altos is deliberately staying out of the public eye, but insiders suggest they're aiming for clinical programs within 3-5 years. Given the funding and talent, they can move fast.

Investment case: Not publicly traded and unlikely to IPO soon given massive private funding. However, watch for acquisition rumors or eventual IPO. If you're an accredited investor, future funding rounds might be accessible through specialized funds investing in longevity biotech.

Risks: Reprogramming could cause cancer (c-Myc is an oncogene), uncontrolled cell proliferation, loss of cell identity if reprogramming goes too far, immune rejection of reprogrammed cells, and the fundamental uncertainty of translating mouse aging results to humans (mouse aging ≠ human aging in many ways).

Takeaways

• Verve Therapeutics (VERV) offers the most immediate investment opportunity with publicly traded stock, Phase 1b proof-of-concept showing 55% LDL reduction from one-time gene editing injection, and Phase 2/3 catalysts coming 2026-2027 that could validate or destroy the $1-2B valuation.

• Fauna Bio represents high-risk, long-timeline potential using hibernating animal genomics to discover drug targets for metabolic and age-related diseases, currently private with preclinical programs and pharma partnerships but 5-10 years from commercialization.

• Altos Labs is the moonshot play backed by $3 billion pursuing cellular reprogramming to reverse aging with Nobel laureates leading research, but not publicly investable, years from clinical trials, and facing enormous safety risks despite transformative potential if successful.