Upstream Bio, Inc. (UPB): A Bull Case Theory

We came across a bullish thesis on Upstream Bio, Inc. on Value investing subreddit by Dizzy_Drawing_2451. In this article, we will summarize the bulls’ thesis on UPB. Upstream Bio, Inc.'s share was trading at $19.97 as of September 5th.

Upstream Bios (UPB) is developing Verekitug, a long-acting TSLP receptor-targeted biologic that could reshape treatment in chronic respiratory diseases, including severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and COPD. Unlike competitors such as Dupixent (every two weeks) and Tezspire (monthly), Verekitug is designed for dosing once every three to six months, significantly improving compliance. The drug also has broader patient applicability than most biologics, which are restricted to biomarker-defined subgroups, enhancing its commercial potential.

September 2025 Phase 2 CRSwNP results showed Verekitug was as effective, if not superior, to Tezspire and Dupixent, with the added benefit of extended dosing. This has de-risked the program considerably and positions it as potentially best-in-class ahead of pivotal Phase 3 trials expected in 2026. The asthma trial, with 666 patients, will provide clarity on whether three- or six-month dosing is optimal. Despite these developments, UPB trades at a ~$1B market cap, well below peers with similar Phase 2 profiles, even though it has nearly $400M in cash to fund operations through 2027. Comparable names like Viking and CellDex trade at $1.5–3B, while GSK acquired Bellus for $2B on less proven data.

Big Pharma interest appears likely, as AstraZeneca’s Tezspire has already validated the TSLP pathway, and Verekitug offers differentiation through receptor targeting. Patent protection into the 2040s extends exclusivity, creating a potential multi-decade franchise. With peak sales estimates exceeding $10B in the U.S. alone and significant ex-U.S. upside, Verekitug could support a $14B+ valuation on risk-adjusted metrics. While biotech carries inherent risks, the combination of best-in-class potential, long-duration IP, and undervalued market cap creates a compelling setup with 2–5x upside on continued progress, and potentially 10x on acquisition.

Previously we covered a bullish thesis on Bio-Techne Corporation (TECH) by scuttleblurb in May 2025, which highlighted its strong legacy in recombinant proteins, expansion into antibodies, assays, and CGT solutions, and recovery signs in organic growth and instrument sales after post-COVID and China headwinds. The company’s stock price has appreciated approximately by 13.51% since our coverage. This is because the thesis played out. Dizzy_Drawing_2451 shares a similar view on industry opportunity but emphasizes on UPB’s Verekitug, a differentiated long-acting biologic in respiratory diseases.

Upstream Bio, Inc. is not on our list of the 30 Most Popular Stocks Among Hedge Funds. As per our database, 21 hedge fund portfolios held UPB at the end of the first quarter which was 19 in the previous quarter. While we acknowledge the potential of UPB as an investment, we believe certain AI stocks offer greater upside potential and carry less downside risk. If you're looking for an extremely undervalued AI stock that also stands to benefit significantly from Trump-era tariffs and the onshoring trend, see our free report on the best short-term AI stock.

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Disclosure: None.