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While focused on oncology, Yosemite's portfolio company Tune Therapeutics is using epigenetic editing to develop a functional cure for Hepatitis B. This is a strategic cancer play, as chronic Hepatitis B is the leading global cause of liver cancer.

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Similar to aging, cancer is a state where cells lose their original identity. By applying age-reversal technologies, cancer cells can be forced to become normal again or even self-destruct, offering a novel approach to cancer treatment.

Observing that allogeneic ('off-the-shelf') cell therapies have not yet achieved their expected impact, Kite Pharma is strategically investing in in vivo approaches. Through acquisitions and partnerships, they are focusing on technologies that edit cells directly within the body, which have shown promising 'autologous-like' results.

Unlike traditional biotech VCs, Yosemite allocates a quarter of its fund to digital health. This reflects its mission to reduce cancer mortality across the entire patient journey, funding solutions for pricing transparency, financial toxicity, and post-approval care.

While other cancers had higher mutation prevalence, Iterion Therapeutics selected hepatocellular carcinoma (HCC) because of the dramatic drop-off in effective treatments after first-line therapy. This created a clear unmet need and a potential for a faster, smaller registration study, demonstrating a savvy commercial strategy.

Many blood cancers are better understood as "regulatory problems" driven by epigenetic failures—the systems controlling which genes are turned on or off. This shifts the therapeutic focus from targeting DNA mutations to developing drugs, like IDH inhibitors, that correct these underlying control mechanisms.

Yosemite's oncology focus stems from Reed Jobs' experience with his father Steve Jobs' pancreatic cancer. However, the firm deliberately adopts a broad, pan-cancer investment strategy, recognizing the interconnectedness of cancer biology across different tissue types.

Despite big pharma's focus on scalable RNA technologies, Series A funding shows a surprising resurgence in investment for cell and gene therapy. This suggests early-stage VCs see significant unsolved value in areas like targeted delivery and gene editing, bucking the broader clinical and commercial narrative.

Earli's technology delivers a genetic blueprint, not a drug. A lipid nanoparticle inserts a DNA-based "switch" that programs cancer cells to produce complex therapeutic payloads locally. This solves the dual problems of systemic drug dilution and off-tumor side effects, aiming to significantly raise the therapeutic index for potent therapies.

Instead of searching for elusive natural markers to target, EARLI's platform creates its own. It programs synthetic genetic "switches" that activate only inside cancer cells, turning them into factories that produce their own cancer-fighting therapies. This shifts the paradigm from biological discovery to biological engineering.

Beam's platform strategy extends beyond diseases with one common mutation. They believe that as regulators accept the base editing platform's consistency, they can efficiently create customized therapies for diseases with numerous rare mutations. This shifts the model from one drug for many patients to a platform that rapidly generates many unique drugs.

Yosemite-Backed Tune Therapeutics Applies Epigenetic Editing to Fight Hepatitis B, a Major Cancer Driver | RiffOn