2 Stocks Up Over 600% in the Past 3 Years With More Room to Run

Summit Therapeutics is positioning to disrupt checkpoint-inhibitor dominance with ivonescimab, a bispecific antibody licensed from Akeso that beat Keytruda in a China phase‑3 NSCLC trial (not usable for FDA) and is now in U.S. phase‑3 studies for lung and colorectal cancer; analysts forecast wide-ranging peak sales (from $4.4bn by 2030 to as high as $53bn), the drug has U.S. patent protection to 2039, and the company’s $13.8bn market cap now largely hinges on upcoming late‑stage data and regulatory filings. Madrigal Pharmaceuticals, meanwhile, has converted regulatory progress into commercial momentum with Rezdiffra—the first FDA‑approved MASH therapy—posting Q3 revenue of $287.3m (up 35% QoQ, 362% YoY) and 29,500 patients on therapy versus a U.S. specialist target of ~315,000; the drug has EU approval, ongoing label‑expansion and combination plans (including a licensed oral GLP‑1), and U.S. patent protection to 2045, but remains on accelerated approval and faces competition from agents like Wegovy, so confirmatory trials and market execution will determine upside.

Analysis

Summit Therapeutics' lead asset, ivonescimab (licensed from Akeso), reported a China phase‑3 win versus Keytruda in PD‑L1‑high NSCLC but that data cannot be used for U.S. approval; the program is in U.S. phase‑3 trials for lung and colorectal cancer, analysts model worldwide sales ranging from $4.4 billion by 2030 to peak forecasts as high as $53 billion, Keytruda generated $29.5 billion last year, and ivonescimab has U.S. patent protection through 2039 while Summit's market capitalization is about $13.8 billion and has eased this year. Positive late‑stage data and successful regulatory filings are the primary value drivers, so share appreciation is likely to be event‑driven and binary in nature until those milestones materialize. Madrigal Pharmaceuticals converted regulatory progress into commercial traction with Rezdiffra, which generated $287.3 million in Q3 revenue (up 35% QoQ and 362% YoY) and has 29,500 patients on therapy versus a U.S. specialist target of ~315,000; Rezdiffra also has EU approval, potential label expansions (including cirrhosis), an added oral GLP‑1 candidate for combination strategies, and U.S. patent protection to 2045. The principal risk to Madrigal is its accelerated approval pathway — confirmatory trials are required — and competitive pressure from agents such as Wegovy; current uptake suggests physician confidence but penetration remains <10% of the targeted specialist population. Market sentiment is moderately positive (per the signals) with higher conviction on MDGL than SMMT, implying nearer‑term upside visibility for Madrigal versus a higher‑beta, milestone‑dependent upside for Summit.

Key Decisions for Investors

• Consider a limited, event‑driven position in Summit Therapeutics ahead of U.S. phase‑3 readouts and regulatory filings, size exposure for binary clinical risk given the $13.8bn market cap and pending pivotal data
• Lean overweight on Madrigal if you have conviction in execution, supported by Q3 Rezdiffra revenue of $287.3m, 29,500 patients and EU approval, but monitor confirmatory trial progress under accelerated approval and competition from Wegovy
• Use milestone‑based rebalancing and consider option hedges or tight stops to protect against negative late‑stage data or regulatory setbacks that could materially re‑rate either stock
• Track three near‑term catalysts — ivonescimab U.S. phase‑3 readouts, Rezdiffra confirmatory/label expansion outcomes, and patient penetration versus the ~315,000 target — and reassess positions on those outcomes