“Taking disease by sTORm”: Developing Rapalogs to Extend Healthy Lifespan (Joan Mannick, Tornado Therapeutics)

<p>Joan Mannick, CEO and co-Founder of Tornado Therapeutics, joins the podcast to discuss her company’s exciting mission of developing a new generation of rapalog compounds specifically targeting the TORC1 complex. Rapalogs are analogs of the natural compound rapamycin, which has been shown to extend lifespan and healthspan in animal models by inhibiting the TOR pathway. However, rapamycin has limitations that have prevented its widespread clinical use for aging-related conditions.</p><p>Tornado aims to overcome these limitations by developing a portfolio of novel rapalogs licensed from Novartis, which were specifically designed to be more selective TORC1 inhibitors with improved drug-like properties relative to rapamycin. Early data suggests these compounds may have an improved safety profile and remain effective at treating diseases like cancer.</p><p>In her conversation with host Chris Patil, Dr. Mannick provides an accessible overview of TOR signaling biology and shares insights from her extensive experience developing rapalogs. The discussion covers Tornado’s strategic approach to indications like oncology and viral infections, the process of characterizing their licensed compounds, and notable milestones on the horizon.</p><p>Dr. Mannick provides an insider perspective on a compelling longevity biotech company striving to translate the promise of rapalogs into effective medicines for age-related diseases.</p><p><strong>Key topics:</strong></p><ul><li>An overview of the TOR signaling pathway, the TORC1 and TORC2 complexes, and how the natural compound rapamycin inhibits TOR function.</li><li>The benefits and limitations of using rapamycin/rapalogs clinically, and the need for more selective TORC1 inhibitors with improved drug properties.</li><li>Tornado’s licensing of novel TORC1-specific rapalogs from Novartis, including early safety data.</li><li>Indications that Tornado is initially pursuing, including oncology and viral infection, applying lessons learned about rapalogs over the past decade.</li><li>The