UPB

Company Overview — What Does Upstream Bio, Inc. Do?

We are a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. We are developing verekitug, the only known antagonist currently in clinical development that targets the receptor for Thymic Stromal Lymphopoietin (“TSLP”), a cytokine which is a clinically validated driver of inflammatory response positioned upstream of multiple signaling cascades that affect a variety of immune mediated diseases. Preclinical and clinical data to date demonstrate verekitug’s highly potent inhibition of the TSLP receptor, which we believe will translate to a differentiated product profile, including improved clinical outcomes, substantially extended dosing intervals and the potential to treat a broad spectrum of patients. We have advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (“CRSwNP”) and plan to initiate development in chronic obstructive pulmonary disease (“COPD”). Our experienced team is committed to maximizing verekitug’s unique attributes to address the substantial unmet needs for patients underserved by today’s standard of care. There are six biologics approved for the treatment of severe asthma; three of these are also approved for CRSwNP. One biologic was recently approved for the treatment of COPD. Total estimated biologics sales in 2023 for asthma in the United States, Europe and Japan markets were approximately $7.5 billion. In December 2021, tezepelumab (marketed as Tezspire by Amgen Inc. (“Amgen”) and AstraZeneca PLC (“AstraZeneca”)), a monoclonal antibody targeting the TSLP ligand, not the receptor, was approved by the U.S. Food and Drug Administration (“FDA”) as an add-on maintenance treatment for patients with severe asthma. Tezepelumab is the first and only treatment for severe asthma without any phenotype or biomarker limitation, highlighting the benefit of blocking TSLP signaling early in the inflammatory cascade as compared to other biologics’ mechanisms of action which are further downstream. In May 2024, Amgen and AstraZeneca reported Phase 2a proof-of-concept data for tezepelumab for the treatment of moderate to very severe COPD at the American Thoracic Society (“ATS”) International Conference. This trial reported a reduction in the frequency of COPD exacerbations that has supported advancement of tezepelumab into Phase 3 development for COPD. These clinical data further demonstrate the potential for a TSLP targeted therapy to treat a variety of inflammatory diseases. Despite the availability of existing biologics for severe respiratory disease, there remains a high unmet need that limits the utilization of these therapies, including suboptimal symptom control and frequent dosing intervals. Verekitug is, to our knowledge, the only monoclonal antibody currently in clinical development that targets and inhibits the TSLP receptor. In May 2024, we presented full proof-of-concept data from our multicenter, randomized, double-blind, placebo-controlled Phase 1b multiple ascending dose (“MAD”) clinical trial in asthma patients demonstrating that dosing with verekitug led to rapid and complete TSLP receptor occupancy, and reductions in fractional exhaled nitric oxide (“FeNO,” a disease-related biomarker) and blood eosinophil levels (“eos,” a disease-related biomarker) that were rapid, substantial and sustained for up to 24 weeks after the last dose. This study also demonstrated that verekitug is approximately 300-fold more potent than tezepelumab (based on published tezepelumab data), which, combined with verekitug’s pharmacokinetic (“PK”) profile, enables an extended dosing interval of up to 24 weeks, compared to tezepelumab (four week dosing interval). Furthermore, clinical data from our Phase 1b MAD trial indicate an approximately 50% greater effect on FeNO than has previously been reported for tezepelumab. We have not conducted head-to-head clinical studies of verekitug against tezepelumab, and note that ongoing and future clinical trials for verekitug may produce differing clinical activity and tolerability results. Three Phase 1 clinical trials have been completed for verekitug across a total of 120 participants, including 32 patients with asthma. In these trials, which were not designed to support formal statistical comparisons, verekitug was well tolerated, demonstrated no evidence of clinically meaningful anti-drug antibodies (“ADAs”), and showed a predictable and consistent PK profile with high subcutaneous bioavailability. Although competitive product candidates may be sponsored by organizations with greater financial resources and expertise to support regulatory approval and market acceptance, we believe verekitug, if approved, will be the preferred biologic for the treatment of severe asthma, CRSwNP and COPD based on its extended dosing interval and effect on broadly accepted disease-associated biomarkers. Having established clinical proof-of-concept in asthma, we are currently conducting two separate multi-national, placebo-controlled, randomized Phase 2 clinical trials to investigate the efficacy of two extended dosing intervals of 12 and 24 weeks for patients with severe asthma and 12 weeks for patients with CRSwNP. These trials have been designed using endpoints that, pending interactions with regulatory authorities, could allow data from these trials to support submissions for product approval. Data from these trials are expected in the second half of 2026 for severe asthma and the second half of 2025 for CRSwNP. Based on available data from Phase 1 trials with verekitug, we plan to initiate our first clinical trial in COPD and have commenced planning activities for a Phase 2 clinical trial, including development of a clinical trial protocol and regulatory approval strategy, and expect to dose the first COPD patient in the second half of 2025. Beyond these indications, we believe verekitug has broad potential, and we intend to leverage its unique attributes to develop it as a potential therapy for numerous TSLP-driven diseases. --- Leveraging TSLP biology to address unmet needs in severe asthma, CRSwNP and COPD TSLP overview Verekitug is a monoclonal antibody that targets and inhibits the TSLP receptor. TSLP is a member of a class of epithelial cytokines, also including IL-25 and IL-33, commonly referred to as alarmins. TSLP is primarily produced by epithelial cells, especially in the lung, gastrointestinal tract and skin. Dendritic cells, basophils, mast cells, keratinocytes and fibroblasts also produce TSLP with appropriate stimulation. In response to various environmental triggers, including viruses, bacteria, allergens, chemical irritants and physical injury, TSLP can initiate and amplify a wide range of innate and adaptive immune responses, including supporting epithelial barrier function, dendritic cell activation, type 2 innate lymphoid cell activation and survival, immune cell recruitment, induction of type 2 responses and regulation of B cell function. Beyond type 2 inflammation, data also support a role for TSLP in propagating non-type 2 inflammatory processes, including IL-17 production, modulation of airway structural cells and the promotion of fibrosis. As such, TSLP signaling is a central instigator of multiple downstream biologic pathways relevant to human diseases that are characterized by epithelial inflammation, including asthma, CRSwNP and COPD. The TSLP signaling pathway is well-understood as a contributor to disease-driving proinflammatory pathways and is a clinically and commercially validated target for therapeutic development. Historically, development of biologics for severe asthma and related conditions has focused on type 2 inflammatory cytokines that are activated downstream in the TSLP signaling pathway, for instance IL-4, IL-5 and IL-13. However, in addition to its effect on type 2 inflammation, emerging evidence indicates that TSLP also impacts non-type 2 inflammation, which may result in broader downregulation of pathways relevant to the pathogenesis of multiple inflammatory diseases. We believe verekitug has the potential, if approved, to address unmet needs in multiple diseases characterized by TSLP-driven pathobiology due to the high potency and potential for extended dosing intervals that we have observed in our preclinical and clinical development to date. Only one drug targeting the TSLP pathway has been approved for the treatment of severe asthma. In December 2021, tezepelumab (marketed as Tezspire by Amgen and AztraZeneca), a monoclonal antibody targeting the TSLP ligand, was approved by the FDA as an add-on maintenance treatment for patients with severe asthma. Tezepelumab is the first and only treatment for severe asthma without any phenotype or biomarker limitation, highlighting the benefit of blocking TSLP signaling early in the inflammatory cascade as compared to other biologics’ mechanisms of action which are further downstream. In the Phase 3 clinical trial of tezepelumab in adults and adolescents with severe, uncontrolled asthma, patients who received tezepelumab had fewer exacerbations and better lung function, asthma control and health-related quality of life than those who received placebo. Based on pooled safety data from the clinical trials of tezepelumab, Tezspire’s FDA approved label identifies hypersensitivity reactions following administration as a clinically significant adverse reaction, as well as pharyngitis, arthralgia and back pain as additional adverse reactions that occurred at an incidence of greater than or equal to 3% and more common than the placebo group. Furthermore, a Phase 2a clinical trial for tezepelumab in COPD patients, which demonstrated a clinically-significant reduction of COPD exacerbations, the most frequently reported adverse events for tezepelumab were worsening of COPD (12.1%) and incidents of COVID-19 infections (14.5%, trial commenced in July 2019), demonstrating a safety and tolerability profile consistent with that observed for tezepelumab in severe asthma. These clinical data further demonstrate the potential for a TSLP targeted therapy to treat a variety of inflammatory diseases. Severe asthma Asthma is a common respiratory disease characterized by chronic airway inflammation that is often underdiagnosed and under-treated. For some people, asthma can simply be a nuisance, for others it can interfere with daily life and potentially even be life-threatening. Of the more than 25 million Americans living with asthma, it is estimated that 5% to 10% suffer from severe asthma. Severe asthma is defined as asthma that remains uncontrolled despite optimized treatment with high-dose inhaled corticosteroids or that requires high-dosed inhaled corticosteroids to prevent symptoms from becoming uncontrolled. It is estimated that approximately 90% of people with severe asthma are eligible for biologics, but only 440,000 patients are currently treated with biologics, suggesting more than 80% of eligible patients are not being optimally treated. U.S. sales in 2023 of biologics for the treatment of severe asthma is estimated to be approximately $6.0 billion. These statistics show there is a large population of people living with uncontrolled symptoms of severe asthma. Key areas of unmet need for people living with severe asthma include improved control of exacerbations and symptoms and reduced treatment burden (e.g. need for frequent injections). Chronic rhinosinusitis with nasal polyps (CRSwNP) CRSwNP is an inflammatory disease of the upper airway, marked by chronic sinonasal inflammation and the presence of inflammatory polyps in the nasal passages and paranasal sinuses. It is estimated by Sanofi that approximately 900,000 patients in the United States and Europe suffer from CRSwNP. Nasal polyps are associated with significant morbidity and debilitating symptoms; it is estimated that 40% to 45% of people with severe asthma also have CRSwNP and that up to 65% of people with CRSwNP also have asthma, demonstrating a strong association between the two conditions. The current treatment options for patients with CRSwNP are corticosteroids, surgery and, more recently, biologics. Although a treatment option, surgery does not guarantee symptom relief. Even with surgery, many people with CRSwNP remain symptomatic, with the recurrence rate of CRSwNP ranging from 20% to 60% within 18 months to four years and increasing to 79% after 12 years. Recurrence is particularly common for people with severe disease, including those also living with asthma or who have undergone prior surgeries. The recent FDA approvals of biologic treatments for CRSwNP have established a well-understood regulatory pathway and route to commercialization. It is estimated that approximately 200,000 adult patients in the United States, major European markets and Japan with CRSwNP are eligible for biologics. Despite these available treatments, the quality of life studies and post-surgical recurrence rates clearly show that many people with CRSwNP have uncontrolled symptoms that are impacting their daily life and current treatments are not meeting their needs. Chronic obstructive pulmonary disease (COPD) Similar to asthma, COPD is a chronic inflammatory disease that obstructs airflow from the lungs. Chronic inflammation causes structural changes within the lungs, narrowing already small airways and damaging lung parenchyma which causes air sacs to lose functionality and decreases lung elasticity. It is typically caused by long-term exposure to irritants, most often cigarette smoke. People with a history of asthma are also more likely to have COPD. Historically, COPD has been considered to have elements of both type 2 and non-type 2 immune responses. COPD is the third leading cause of death worldwide, causing approximately 3.2 million deaths in 2019. Almost 14.2 million Americans, or 6.5% of the adult population, reported they have been diagnosed with COPD, yet the actual number is likely higher given that more than half of adults with low pulmonary function were not aware that they had COPD. Treatments for COPD are similar to those for asthma and CRSwNP, including inhaled steroids to reduce inflammation in the airways as well as bronchodilator inhalers to relax airways and improve airflow. Oxygen and surgery may also be used for people with severe COPD. Dupilumab (marketed as Dupixent by Sanofi and Regeneron Pharmaceuticals, Inc.), an interleukin-4 receptor alpha antagonist, is the only biologic approved for the treatment of COPD. Despite available treatments, 60% of all COPD patients report some limitations in their daily activity, with 45% being unable to work and 75% complaining of difficulty climbing stairs. Given the high levels of morbidity and mortality associated with COPD, the currently available medicines are not sufficient to control symptoms or disease progression. Verekitug: Inhibiting TSLP signaling in severe asthma, CRSwNP and COPD Verekitug is a novel recombinant fully human immunoglobulin G1 monoclonal antibody that binds to the TSLP receptor and inhibits its signaling. In 2021, we acquired verekitug from Astellas Pharma Inc. (“Astellas”). Astellas discovered the compound and completed preclinical studies and a Phase 1 single ascending dose (“SAD”) trial, providing the early foundational work for our Phase 1b MAD trial. In those preclinical studies, which were not designed to support formal statistical comparisons, verekitug potently inhibited TSLP signaling. Additionally, verekitug inhibited cytokine production from CD4+ T cells, suggesting that it may be effective against type 2 and non-type 2 inflammation. In the Phase 1 SAD trial in 56 healthy volunteers, verekitug demonstrated a favorable safety profile with no drug-related serious treatment-emergent adverse events, dose proportional PK and a pharmacodynamic (“PD”) effect consistent with TSLP antagonism. We have conducted two additional clinical trials of verekitug: a Phase 1b MAD trial in patients with asthma and a Japanese ethnobridging study in healthy volunteers. Across the three clinical trials, we have data from 120 total participants, including 32 patients with asthma. In these trials, verekitug was well tolerated, had no clinically meaningful immunogenicity, and showed a predictable and consistent PK profile with high subcutaneous bioavailability. Our Phase 1b MAD clinical trial, which enrolled 32 adult participants aged 18 to 60 with mild to moderate asthma, established clinical proof-of-concept for verekitug in asthma. In the trial, which was not designed to support formal statistical comparisons, verekitug demonstrated rapid, substantial and sustained target engagement and maintained maximal inhibition of disease-related biomarkers in patients with asthma for up to 24 weeks after the last study dose. Results of the Phase 1b study also demonstrated that verekitug is a potent inhibitor of the TSLP receptor and has the potential for an extending dosing interval compared to currently available treatments. Importantly, the PK/PD modeling that was done based on the preclinical data aligned very closely with these early clinical results, strengthening our understanding of verekitug’s attributes and behavior in humans. We are currently conducting two separate multi-national, placebo-controlled, randomized Phase 2 clinical trials to investigate the efficacy of two extended dosing intervals of 12 and 24 weeks for patients with severe asthma and 12 weeks for patients with CRSwNP. These trials have been designed using endpoints that, pending interactions with regulatory authorities, could allow data from these trials to support submissions for product approval. Data from these trials are expected in the second half of 2026 for severe asthma and the second half of 2025 for CRSwNP. Based on available data from Phase 1 trials with verekitug, we plan to initiate our first clinical trial in COPD and have commenced planning activities for a Phase 2 clinical trial, including development of a clinical trial protocol and regulatory approval strategy, and expect to dose the first COPD patient in the second half of 2025. Beyond these indications, we believe verekitug has broad potential, and we intend to leverage its unique attributes to develop it as a potential therapy for other TSLP-driven diseases. We were incorporated under the laws of the State of Delaware in April 2021 under the name Upstream Bio, Inc. Our principal corporate office is located at 890 Winter Street, Suite 200, Waltham, MA 02451. We have one subsidiary, Upstream Bio Securities Corporation, formed in November 2021 under the laws of the Commonwealth of Massachusetts. Upstream Bio, Inc. (UPB) is classified as a small-cap stock in the Healthcare sector, specifically within the Pharmaceutical Products industry. The company is led by CEO E. Rand Sutherland, headquartered in WALTHAM, Massachusetts. With a market capitalization of $507M, UPB is one of the notable companies in the Healthcare sector.

Upstream Bio, Inc. (UPB) Stock Rating — Reduce (April 2026)

As of April 2026, Upstream Bio, Inc. receives a Reduce rating with a composite score of 27.5/100 and 2 out of 5 stars from the Blank Capital Research quantitative model.UPB ranks #3,466 out of 4,446 stocks in our coverage universe. Within the Healthcare sector, Upstream Bio, Inc. ranks #538 of 838 stocks, placing it in the lower half of its Healthcare peers. The rating is generated by a multi-factor model that weighs quality (30%), momentum (25%), value (15%), investment (10%), stability (10%), and short interest (10%).

UPB Stock Price and 52-Week Range

Upstream Bio, Inc. (UPB) currently trades at $10.49. The stock gained $0.07 (0.7%) in the most recent trading session. The 52-week high for UPB is $33.68, which means the stock is currently trading -68.9% from its annual peak. The 52-week low is $5.14, putting the stock 104.1% above its annual trough. Recent trading volume was 733K shares, suggesting relatively thin trading activity.

Is UPB Overvalued or Undervalued? — Valuation Analysis

Upstream Bio, Inc. (UPB) carries a value factor score of 16/100 in the Blank Capital model, signaling premium valuation that prices in significant future growth. The price-to-book ratio stands at 1.55x, versus the sector average of 2.75x. The price-to-sales ratio is 189.00x, compared to 1.66x for the average Healthcare stock.

At current multiples, Upstream Bio, Inc. trades at a premium to most Healthcare peers. This elevated valuation may be justified if the company can sustain above-average growth rates and profitability, but it also creates downside risk if earnings disappoint expectations.

Upstream Bio, Inc. Profitability — ROE, Margins, and Quality Score

Upstream Bio, Inc. (UPB) earns a quality factor score of 27/100, signaling below-average profitability metrics relative to the broader market. The return on equity (ROE) is -34.4%, compared to the Healthcare sector average of -43.5%, which is below typical expectations for high-quality companies. Return on assets (ROA) comes in at -33.1% versus the sector average of -33.1%.

On a margin basis, Upstream Bio, Inc. reports gross margins of 100.0%, compared to 71.5% for the sector. The operating margin is -4760.2% (sector: -66.1%). Net profit margin stands at -4164.8%, versus -58.7% for the average Healthcare stock. Revenue growth is running at 12.5% on a trailing basis, compared to 10.6% for the sector. Profitability is below benchmark levels, which may reflect industry headwinds, elevated reinvestment, or structural challenges.

UPB Debt, Balance Sheet, and Financial Health

Upstream Bio, Inc. has a debt-to-equity ratio of 4.0%, compared to the Healthcare sector average of 32.0%. The low leverage indicates a conservative balance sheet with significant financial flexibility. The current ratio is 26.15x, indicating strong short-term liquidity. Total debt on the balance sheet is $0. Cash and equivalents stand at $72M.

UPB has a beta of 0.88, meaning it is roughly in line with the broader market in terms of price volatility. The stability factor score for Upstream Bio, Inc. is 28/100, suggesting elevated price swings that may be unsuitable for conservative portfolios.

Upstream Bio, Inc. Revenue and Earnings History — Quarterly Trend

In TTM 2026, Upstream Bio, Inc. reported revenue of $3M and earnings per share (EPS) of $-2.66. Net income for the quarter was $-117M. Gross margin was 100.0%. Operating income came in at $-133M.

In FY 2025, Upstream Bio, Inc. reported revenue of $3M and earnings per share (EPS) of $-2.66. Net income for the quarter was $-143M. Revenue grew 20.4% year-over-year compared to FY 2024. Operating income came in at $-160M.

In Q3 2025, Upstream Bio, Inc. reported revenue of $683,000 and earnings per share (EPS) of $-0.63. Net income for the quarter was $-34M. Revenue grew 12.5% year-over-year compared to Q3 2024. Operating income came in at $-38M.

In Q2 2025, Upstream Bio, Inc. reported revenue of $937,000 and earnings per share (EPS) of $-0.74. Net income for the quarter was $-40M. Operating income came in at $-44M.

Over the past 8 quarters, Upstream Bio, Inc. has demonstrated a growth trajectory, with revenue expanding from $2M to $3M. Investors analyzing UPB stock should weigh these quarterly trends alongside the valuation and quality metrics discussed above.

UPB Dividend Yield and Income Analysis

Upstream Bio, Inc. (UPB) does not currently pay a dividend. This is common among smaller companies in the Pharmaceutical Products industry that prefer to reinvest cash flows into business expansion rather than returning capital to shareholders. Income-focused investors looking for Healthcare dividend stocks may want to explore other Healthcare stocks or use the stock screener to filter by dividend yield.

UPB Momentum and Technical Analysis Profile

Upstream Bio, Inc. (UPB) has a momentum factor score of 21/100, signaling weak relative price performance. Stocks with low momentum scores have historically tended to continue underperforming in the near term. The investment factor score is 25/100, which measures capital allocation efficiency and asset growth patterns. The short interest score of 62/100 reflects moderate short selling activity.

UPB vs Competitors — Healthcare Sector Ranking and Peer Comparison

Within the Healthcare sector, Upstream Bio, Inc. (UPB) ranks #538 out of 838 stocks based on the Blank Capital composite score. This places UPB in the lower half of all Healthcare stocks in our coverage universe. Key competitors and sector peers include ASTRAZENECA PLC (AZN) with a score of 61.4/100, Sol-Gel Technologies Ltd. (SLGL) with a score of 56.6/100, VIEMED HEALTHCARE, INC. (VMD) with a score of 53.4/100, Innoviva, Inc. (INVA) with a score of 52.7/100, and JOHNSON & JOHNSON (JNJ) with a score of 51.7/100.

Comparing UPB against the S&P 500 benchmark is also instructive for understanding relative performance. Investors can view the full UPB vs S&P 500 (SPY) comparison to assess how Upstream Bio, Inc. stacks up against the broader market across all factor dimensions.

UPB Next Earnings Date

No upcoming earnings date has been announced for Upstream Bio, Inc. (UPB) at this time. Check the earnings calendar for the latest scheduling updates across all stocks in our coverage universe.

Should You Buy UPB? — Investment Thesis Summary

The quantitative profile for Upstream Bio, Inc. suggests caution. The quality score of 27/100 flags below-average profitability. The value score of 16/100 indicates premium valuation. Momentum is weak at 21/100, a headwind for near-term performance. High volatility (stability score 28/100) increases portfolio risk.

In summary, Upstream Bio, Inc. (UPB) earns a Reduce rating with a composite score of 27.5/100 as of April 2026. The rating is derived from the Blank Capital Research methodology, which combines six factor dimensions into a single quantitative ranking. Investors should consider these quantitative signals alongside their own fundamental research, risk tolerance, and investment time horizon before making buy or sell decisions on UPB stock.

Related Resources for UPB Investors

Explore more research and tools: UPB vs S&P 500 comparison, top Healthcare stocks, stock screener, our methodology, quality factor explained, value factor explained, momentum factor explained. Compare UPB head-to-head with peers: UPB vs AZN, UPB vs SLGL, UPB vs VMD.