Here are 1-2 brief analogies for Upstream Bio:

• Upstream Bio is developing a drug that aims to be **the 'long-acting Tezspire'**, promising significantly less frequent injections (every 24 weeks) and higher potency for severe asthma and other inflammatory diseases, compared to Amgen and AstraZeneca's Tezspire.
• Think of them as **a specialized biotech trying to 'one-up' Amgen and AstraZeneca** in the TSLP-targeting space, with a drug designed for superior potency and patient convenience.

• Verekitug: A clinical-stage monoclonal antibody designed to inhibit the TSLP receptor for the treatment of inflammatory diseases, including severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD).

Upstream Bio (UPB) is a clinical-stage biotechnology company focused on developing treatments for inflammatory diseases. The company is currently advancing its lead product candidate, verekitug, through Phase 2 clinical trials for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), and plans to initiate a Phase 2 trial for chronic obstructive pulmonary disease (COPD).

As a clinical-stage company, Upstream Bio does not yet have any commercialized products approved for sale. Therefore, it does not currently have major customers, either other companies or individual patients, from which it derives product revenue. Its current activities are focused on research and development, conducting clinical trials, and pursuing regulatory approvals for its drug candidate, verekitug.

Rand Sutherland, MD, Chief Executive Officer

Dr. Sutherland has over 25 years of business and clinical experience. He most recently served as CEO of Seeker Biologics and previously as President of Translate Bio, Inc. before its acquisition by Sanofi. Prior to that, Dr. Sutherland held various R&D and medical affairs roles at Sanofi, leading the development of new medicines in Immunology and Rare Diseases and heading global medical affairs for the Specialty Care business unit.

Mike Gray, MBA, Chief Financial Officer and Chief Operating Officer

Mr. Gray brings more than 25 years of public-private leadership experience. He was most recently the CFO and COO of Carmot Therapeutics, where he played a role in securing the company's acquisition by Roche in 2024. Before Carmot, he held CFO and COO positions at Imara and Arsanis, assisting both companies with initial public offerings and organizational development.

Aaron Deykin, MD, Chief Medical Officer & Head of R&D

Dr. Deykin leads Upstream Bio's clinical development activities and strategy. Before joining Upstream, he was Senior Vice President and Head of Clinical Sciences at Biogen, overseeing clinical development in immunology, fibrosis, and neurology. He also previously served as Assistant Professor of Medicine at Harvard Medical School and was a faculty member at Brigham and Women's Hospital.

Adam Houghton, PhD, Chief Business Officer

Dr. Houghton is responsible for Business Development and Pipeline Strategy at Upstream Bio. Prior to this role, he was Vice President, Corporate Strategy, and Head of AbbVie Ventures, AbbVie's corporate venture investment group. He has also led Search and Evaluation teams at AbbVie, Biogen, and Eli Lilly, contributing significantly to major licensing and acquisition deals in Immunology and Neuroscience.

Stacy Price, MS, PMP, Chief Technology Officer

Ms. Price has served as Chief Technology Officer of Upstream Bio since May 2025, overseeing the company's technical operations and product development. She has over 25 years of leadership experience in technical operations within the biotechnology industry, having previously served as Chief Technology and Manufacturing Officer at Invivyd.

Risk of Clinical Trial Failure and Regulatory Approval: Upstream Bio's success is entirely dependent on the successful outcome of its ongoing and planned Phase 2 clinical trials for verekitug in severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD), as well as subsequent regulatory approvals. The company explicitly states that "ongoing and future clinical trials for verekitug may produce differing clinical activity and tolerability results" and that the trial designs "pending interactions with regulatory authorities, could allow data from these trials to support submissions for product approval," indicating that approval is not guaranteed. Failure to demonstrate efficacy, safety, or to receive regulatory clearance would severely impact the company's business prospects.

Competition from Established Therapies and Companies: Verekitug faces significant competition, particularly from tezepelumab (Tezspire), which is already approved for severe asthma and is marketed by large pharmaceutical companies, Amgen Inc. and AstraZeneca PLC, with greater financial resources and expertise. Tezepelumab also targets the TSLP pathway and is advancing in Phase 3 development for COPD. Additionally, there are six other biologics approved for severe asthma, three of which are also approved for CRSwNP, and dupilumab is approved for COPD, creating a crowded market. Upstream Bio has not conducted head-to-head clinical studies against tezepelumab, and its claims of differentiation, such as higher potency and extended dosing, would need to be convincingly demonstrated to gain market share against established players.

Dependence on a Single Product Candidate: Upstream Bio's business is currently focused solely on the development and potential commercialization of verekitug. The company's entire value and future prospects are tied to the success of this single monoclonal antibody across its target indications. Any setbacks, failures, or unexpected issues related to verekitug in clinical development, regulatory approval, or commercialization would have a profound and potentially catastrophic impact on the company.

The rapid advancement of tezepelumab (marketed as Tezspire by Amgen and AstraZeneca) into Phase 3 clinical development for the treatment of chronic obstructive pulmonary disease (COPD) following positive Phase 2a data, positioning a well-resourced competitor significantly ahead of Upstream Bio's planned Phase 2 initiation for verekitug in COPD in the second half of 2025.

• The estimated biologics sales for asthma in the United States, Europe, and Japan markets were approximately $7.5 billion in 2023.
• The estimated U.S. sales of biologics for the treatment of severe asthma were approximately $6.0 billion in 2023.

Expected Drivers of Future Revenue Growth for Upstream Bio (UPB)

• **Potential Market Entry in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP):** Upstream Bio anticipates data from its Phase 2 clinical trial for verekitug in CRSwNP during the second half of 2025. Successful trial outcomes and subsequent regulatory approval would pave the way for market entry within the next 2-3 years, targeting a significant patient population in the United States, Europe, and Japan.
• **Potential Market Entry in Severe Asthma:** Data from the multi-national, placebo-controlled, randomized Phase 2 clinical trials for verekitug in severe asthma are expected in the second half of 2026. Positive results and regulatory approval would allow Upstream Bio to enter the substantial severe asthma market, which had estimated biologics sales of approximately $6.0 billion in the U.S. in 2023.
• **Expansion into the Chronic Obstructive Pulmonary Disease (COPD) Market:** Upstream Bio plans to initiate its first clinical trial in COPD, with the first patient expected to be dosed in the second half of 2025. This strategic move into the large COPD market, where only one biologic is currently approved, represents a significant long-term revenue growth opportunity, with early phase success potentially driving valuation within the 2-3 year timeframe.
• **Differentiated Product Profile of Verekitug:** Verekitug's highly potent inhibition of the TSLP receptor and its potential for substantially extended dosing intervals (up to 24 weeks compared to competitors) are expected to be key drivers of market adoption and share capture once approved. This differentiated profile is anticipated to translate into improved clinical outcomes and a preferred treatment option for patients in severe asthma, CRSwNP, and eventually COPD, accelerating revenue growth.

Outbound Investments

• In 2021, Upstream Bio acquired verekitug from Astellas Pharma Inc.