Rion found that culturing stem cells in a lab to force division leads to rapid DNA damage, as cells are not designed for this artificial environment. This damage created inconsistent exosome products, making large-scale, uniform manufacturing from stem cells unfeasible and prompting a search for a more stable source.

Breakthrough drugs aren't always driven by novel biological targets. Major successes like Humira or GLP-1s often succeeded through a superior modality (a humanized antibody) or a contrarian bet on a market (obesity). This shows that business and technical execution can be more critical than being the first to discover a biological mechanism.

Nobel Prize-winning research identified genes (Yamanaka factors) that revert specialized adult cells back into their embryonic, stem-cell state. This discovery proves cellular differentiation and aging are not irreversible, opening the door for regenerative therapies by "rebooting" cells to an earlier state.

In stark contrast to the US, Chinese investors are accelerating funding for early-stage cell and gene therapies, which now account for 29% of seed/Series A rounds. These firms are specifically backing technologies like NK cell therapies, which have fallen out of favor in the West, creating a divergent global innovation strategy.

Rion strategically chose diabetic foot ulcers as its lead indication to de-risk its new therapeutic class. This "outside-in" approach allows the company to build a substantial safety record and gain regulatory and clinical acceptance with a topical product before advancing to more complex systemic applications.

CZI set an audacious goal to cure all disease. When scientists deemed it impossible, CZI's follow-up question, "Why not?" revealed the true bottleneck wasn't funding individual projects, but a systemic lack of shared tools, which then became their core focus.

Rion avoids disrupting the medical platelet supply by sourcing near-expiration units from blood banks. This provides an abundant, low-cost raw material. In return, blood banks gain a revenue stream for products that would be discarded, encouraging them to maintain larger inventories for transfusions, creating a win-win.

To save money, Rhythm's leadership considered canceling a clinical study because the prevailing scientific logic suggested their drug wouldn't work. The study's unexpected, resounding success became the company's pivotal turning point, highlighting the value of pursuing scientifically contrarian ideas.

Unlike many cell therapies, Rion's platelet-derived exosomes are devoid of the self/non-self surface markers that trigger immune rejection. This "immune privilege" is a critical biological advantage, allowing the product to be used as a universal, off-the-shelf therapy for any patient without needing donor matching.