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While shares in Upstream fell 5.55% in premarket trading, the biotech\'s stock shot up nearly 20% to $20.26 by the end of the day Tuesday.\n Upstream Bio has sailed to a phase 2 win in sinusitis and plans to push its candidate forward against a competitive current.Investigators randomized 81 adults with chronic rhinosinusitis with nasal polyps (CRSwNP) to receive the anti-TSLP antibody verekitug or placebo every 12 weeks. After 24 weeks, Upstream linked the study drug to a 1.8-point placebo-adjusted reduction in endoscopic nasal polyp score (NPS) compared with baseline. The result caused the trial to meet its primary endpoint.Upstream posted hits on secondary endpoints, too. The biotech linked verekitug to a 0.8-point placebo-adjusted reduction from baseline in the patient-reported nasal congestion score (NCS). Upstream also hailed significant improvements in the need for systemic corticosteroids or nasal polyp surgeries and in total symptom scores. With no serious adverse events reported, the biotech believes it has the data to support talks with regulatory agencies about further development of verekitug. Upstream used phase 2 efficacy endpoints that, pending talks with regulators, could produce data to support submissions for approval. The biotech is advancing toward a market already served by Genentech and Novartis’ Xolair, Sanofi and Regeneron’s Dupixent (dupilumab) and GSK’s Nucala. Amgen and AstraZeneca have also filed for approval of TSLP drug Tezspire in the indication. While Tezspire targets the TSLP ligand, verekitug blocks the receptor. Upstream claims verekitug is about 300 times more potent than Tezspire.The emergence of a set of biologic treatments for CRSwNP over the past five years has set the bar verekitug needs to clear to compete. Asked about expectations for the phase 2 trial, Upstream CEO Rand Sutherland, M.D., quoted data on dupilumab.“Look at the label for dupilumab. There\'s about a 2-point change in the endoscopic nasal polyps score that was reported there. We think that that\'s probably relatively a floor for efficacy that we would want to see to be competitive,” Sutherland said at the J.P. Morgan Healthcare Conference in January. “I mean, there’s a little bit of room around that. We’ve powered to be even a little bit more robust than that.” Verekitug could have an advantage even if it only matches the efficacy of existing biologics. The antibody was given every 12 weeks in the phase 2 trial, while Dupixent and Tezspire were given every two weeks and every four weeks, respectively, in their phase 3 CRSwNP trials. Upstream’s market research found about 90% of patients would consider switching to a product with a less frequent dosing interval.William Blair analysts said the data drop \"largely comes in line with data from Tezspire, which showed roughly a 1.7-point improvement over placebo at week 24 that further improved to 2.07 at week 52.\" A sensitivity analysis of Upstream\'s results censoring patients receiving rescue steroids would boost the treatment difference to 1.9 points on the primary endpoint, likely surpassing Tezspire results at a similar timepoint, the analysts wrote in a Sept. 2 note. While shares in Upstream fell 5.55% in premarket trading, the biotech\'s stock shot up nearly 20% to $20.26 by the end of the day Tuesday. Upstream went public 11 months ago in an IPO that grossed $293 million. The biotech sold shares for $17 each in its IPO.Editor\'s note: This story has been corrected to include more than premarket trading changes.

Upstream Bio reported Tuesday that its experimental antibody verekitug hit the main goals of a mid-stage study in chronic rhinosinusitis with nasal polyps (CRSwNP) as the biotech looks to bolster its case that blocking the TSLP receptor could provide an edge over existing drugs.Amgen and AstraZeneca's Tezspire (tezepelumab-ekko), which blocks the TSLP ligand, is already under regulatory review for nasal polyps, putting it ahead of verekitug in a field that also includes established biologics such as Sanofi and Regeneron Pharmaceuticals' IL-4/IL-13 receptor blocker Dupixent (dupilumab), GSK's IL-5 antagonist Nucala (mepolizumab), and Roche and Novartis' anti-IgE antibody Xolair (omalizumab).Upstream is hoping to elbow its way into the market with a different approach – targeting the TSLP receptor instead of the ligand.Quarterly dosingThe 81-patient VIBRANT trial showed that a 100-mg subcutaneous dose given once every 12 weeks led to a placebo-adjusted drop of 1.8 points in endoscopic nasal polyp score (NPS) at the 24-week mark, compared to baseline, meeting the primary endpoint. Patients also reported less nasal congestion, with scores improving by 0.8 points compared to placebo, significant improvements in sinus opacification and a 76% reduction in the need for surgery or systemic corticosteroids. No serious safety concerns emerged."These results reinforce our earlier observations that verekitug's high potency, achieved through targeting the TSLP receptor, has the potential to translate into clinical attributes distinct from those offered by any currently available therapy," said Aaron Deykin, the company's chief medical officer and R&D head.Upstream has cited Phase Ib data suggesting that its receptor strategy may be about 300-fold more potent than Tezspire, while allowing for an extended dosing interval of up to six months.Dupixent, given every-other-week, is a commercial leader in the CRSwNP space, while Amgen and AstraZeneca are seeking approval for monthly Tezspire for the condition following the Phase III WAYPOINT readout in March. Meanwhile, aside from Nucala, GSK is also advancing depemokimab, an IL-5-targeting antibody with twice-yearly dosing. For insight into the competitive landscape, see – Spotlight On: More momentum for Tezspire? — AstraZeneca and Amgen's biologic therapy delivers compelling rhinosinusitis data.

– Pharmacology modeling data presented at the European Academy of Allergy & Clinical Immunology (EAACI) Congress describe mechanistic insights for greater potency with verekitug compared to tezepelumab – – Supports potentially differentiated profile of verekitug across a broad range of inflammatory diseases, including severe asthma, chronic obstructive pulmonary disease (COPD) and chronic rhinosinusitis with nasal polyps (CRSwNP) – WALTHAM, MA, USA I June 15, 2025 I Upstream Bio, Inc. (Nasdaq: UPB), a clinical-stage company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders, today announced the presentation of translational pharmacology modeling data supporting verekitug’s Thymic Stromal Lymphopoietin (TSLP) receptor targeting as a mechanism for greater potency when compared to treatments targeting the TSLP ligand. Data were presented at the European Academy of Allergy & Clinical Immunology (EAACI) Congress taking place June 13-16, 2025, in Glasgow, United Kingdom. TSLP is a cytokine that is a key driver of the inflammatory response in major allergic and inflammatory diseases, such as asthma, where disruption of TSLP signaling has been clinically validated as an effective treatment approach. Because TSLP is a target upstream in the inflammatory cascade, blocking the TSLP receptor presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases. Upstream is developing verekitug in multiple severe respiratory diseases including severe asthma, COPD, and CRSwNP. Verekitug is the only monoclonal antibody currently in clinical development that targets and inhibits the TSLP receptor. “These data reinforce our belief in the differentiated profile of verekitug, as the model elucidates important biologic parameters that drive the differentiated rapid, substantial and sustained treatment effects observed through TSLP receptor inhibition with verekitug,” said Aaron Deykin, MD, Chief Medical Officer and Head of Research & Development of Upstream Bio. “We look forward to further assessing the potential translation of this unique mechanism into clinical benefit in patients with severe respiratory diseases, first with top-line Phase 2 clinical data in CRSwNP in the third quarter of this year followed by data in severe asthma in the first half of 2026.” Data presented used an in silico system pharmacology modeling approach to provide a mechanism-based understanding for the observed potency of verekitug and are summarized as follows: A digital version of the presentation can be found on the Upstream Bio website . About TSLP and TSLPR Blockade Thymic Stromal Lymphopoietin (TSLP) is a cytokine that is a key driver of the inflammatory response in major allergic and inflammatory diseases, such as asthma, where disruption of TSLP signaling has been clinically validated as an effective therapeutic strategy. TSLP activation is one of the first events in the inflammatory cascade stimulated by allergens, viruses and other triggers, initiating the activation of downstream targets such as IL-4, IL-5, IL-13, IL-17 and IgE. Because TSLP is a target upstream in the inflammatory cascade, blocking the TSLP receptor (TSLPR) presents an opportunity for a single treatment to impact the drivers of multiple pathological inflammatory processes across a broad set of diseases. About Verekitug Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to the TSLP receptor and inhibits proinflammatory signaling initiated by TSLP. It is the only monoclonal antibody currently in clinical development that targets and inhibits the TSLP receptor. Verekitug is currently being evaluated in two separate multi-national, placebo-controlled, randomized Phase 2 clinical trials, the VALIANT trial in patients with severe asthma (NCT06196879) and the VIBRANT trial in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT06164704). Upstream Bio is also initiating a Phase 2 clinical trial (NCT06981078) of verekitug in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In preclinical studies, verekitug demonstrated high occupancy of the TSLP receptor and potent inhibition of TSLP signaling. Additionally, verekitug inhibited cytokine production from both CD4+ T cells and ILC2 cells and completely suppressed skin allergic reactions in a non-human primate model, suggesting that it may be effective against multiple types of inflammation. Three clinical trials have been completed for verekitug, including a Phase 1 single-ascending dose (SAD) clinical trial and a Phase 1b multiple-ascending dose (MAD) clinical trial. In these trials, verekitug was well tolerated, had no clinically meaningful immunogenicity, and showed a predictable and consistent pharmacokinetic profile and high subcutaneous bioavailability. About Upstream Bio Upstream Bio is a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. The Company is 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. The Company has advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps and is initiating development in chronic obstructive pulmonary disease. Upstream Bio’s team is committed to maximizing verekitug’s unique attributes to address the substantial unmet needs for patients underserved by today’s standard of care. To learn more, please visit www.upstreambio.com . SOURCE: Upstream Bio