TSLP

Upstream Bio is joining a recent swell of biotechs going public. The fall flurry of biotech IPOs shows no signs of abating, with Upstream Bio becoming the latest company to express an intention to go public.The Waltham, Massachusetts-based biotech has yet to set expectations on the size of its proposed offering, but said in a Securities and Exchange Commission filing yesterday that the proceeds would be directed toward its lead asset verekitug.The company has pitched verekitug as the “only known antagonist currently in clinical development that targets the receptor for thymic stromal lymphopoietin (TSLP).” This cytokine is a known driver of the inflammatory response, affecting a range of immune-mediated diseases.Proceeds from the IPO will go in part to completing an ongoing phase 2 trial of the drug in severe asthma, as well as launching a phase 3 study in the same indication. Funds will also be used to continue an ongoing phase 2 study of verekitug in chronic rhinosinusitis with nasal polyps, with plans for a phase 3 to follow. In addition, the biotech has its eye on a potential phase 2 study in COPD.Any remaining cash will be spent on further R&D for verekitug, including expanding into other indications, as well as for working capital and general business costs, according to the filing.The company’s recent clinical efforts have been funded by a $200 million series B last year, which saw Enavate Sciences and Venrock Healthcare Capital Partners lead a group of investors including the likes of Bain Capital Life Sciences, Wellington Management and OrbiMed. That round came just a year after the company hauled in $200 million from a series A as part of its launch in June 2022. The Upstream story can be traced back to 2021, when lead backers OrbiMed and Maruho began building the company around verekitug, an asset won in an auction from Japanese pharma Astellas. Rather than put up a small amount to start off with, OrbiMed, Maruho and other investors provided the new biotech with significant cash to get through its initial stages.The company began with what it described to Fierce Biotech at the time as a “lean and mean” team of 13 people, but yesterday’s filing shows that this workforce had increased to 38 full-time employees by last month.Upstream’s C-suite also received a shake-up (PDF) in April, when Rand Sutherland, M.D., took on the CEO role after having headed up Seeker Biologics—which closed last year—and previously serving as president of Translate Bio prior to its acquisition by Sanofi.Upstream’s intentions are the latest indication that after a summer lull, the biotech IPO scene has picked up pace, with a trio of clinical-stage companies all going public with nine-figure offerings last Friday. They were followed by the smaller-scale IPO of Kairos Pharma on Monday.

Just hours after the US Federal Reserve announced the first interest rate cut in four years , respiratory biotech Upstream Bio revealed plans for a public listing. The Boston-area biotech unveiled its investor prospectus on Wednesday afternoon, saying it plans to trade on the Nasdaq under the ticker $UPB . The biotech is developing a drug called verekitug, a TSLP receptor antagonist, for severe asthma and a form of chronic rhinosinusitis, with plans to go after the large market of chronic obstructive pulmonary disease (COPD). After a chilly few months in the market, signs of life are emerging with biotech IPOs — and are likely to be helped by falling interest rates. Three companies listed last week , and this week the obesity startup BioAge said it plans to raise about $120 million in an upcoming IPO. William Blair healthcare banker Kevin Eisele told Endpoints News this week that he doesn’t expect “a mad rush out of the gates before year-end, but I do think we’ll see some sustained IPO activity until the new year and likely more in 2025.” The startup’s TSLP target has competition. Amgen and AstraZeneca sell the asthma drug Tezspire, although Upstream said its treatment candidate targets the receptor, a different method than the approved medicine. And Blackstone is betting up to $300 million on a company called Uniquity Bio, which is taking forward a former Merck atopic dermatitis asset, also targeting TSLP, that the company is repositioning for asthma and COPD. Upstream had $235 million in cash, equivalents and short-term investments at the end of June, according to its SEC filing. It disclosed a $200 million Series B in June 2023, about 12 months after disclosing its first $200 million round. It spent $25.7 million on R&D in the first half of this year, about double the $12.4 million it spent developing its drug in the same period last year. Upstream’s biggest shareholder is OrbiMed, which owns about 13%. Other investors with 5% or more are: AI Upstream, Altshuler Shaham Provident Funds and Pension, Decheng Capital, TCG Crossover, HBM Healthcare, Maruho Deutschland, Enavate Sciences, Samsara BioCapital, Omega, Bain Capital Life Sciences and Venrock.

– Treatment with verekitug led to rapid PD effects which were sustained for up to 24 weeks, supporting evaluation of dosing intervals of once every 12 or 24 weeks in ongoing Phase 2 clinical trials – – PK/PD modeling predicts substantially higher clinical potency of verekitug compared to reported tezepelumab data – WALTHAM, Mass., Sept. 09, 2024 (GLOBE NEWSWIRE) -- Upstream Bio, Inc., a clinical-stage company developing verekitug, an investigational antagonist of the Thymic Stromal Lymphopoietin (TSLP) receptor, today presents additional clinical data from its 32-week, Phase 1b multiple ascending dose trial of verekitug (UPB-101) in adults with asthma at the European Respiratory Society (ERS) Congress 2024 being held in Vienna, Austria. New data from pooled verekitug-treated asthma patient cohorts demonstrated substantial reductions in biomarkers of inflammation including IL-5 (Interleukin 5) and IgE (immunoglobin E), in line with previously reported effects on blood eosinophils and fractional exhaled nitric oxide (FeNO). Predictive modeling based on observed pharmacodynamic (PD) and pharmacokinetic (PK) parameters suggests that verekitug may exhibit high potency in asthma patients, with an approximately 1.5-fold greater maximal predicted reduction of FeNO compared to that reported for tezepelumab. PK/PD modeling predicts that verekitug 100 mg once every 12 weeks (Q12W) and 400 mg once every 24 weeks (Q24W) dosing regimens could maintain trough serum levels above FeNO EC90 levels for >95% of the dosing interval, supporting testing of these dosing regimens in the ongoing Phase 2 VALIANT clinical trial for verekitug in severe asthma. As previously reported, verekitug was well tolerated at all dose levels tested. Verekitug also demonstrated rapid and substantial treatment effects, including 100% TSLP receptor occupancy after one dose, up to 54% reduction in FeNO and up to 65% reduction in blood eosinophils at 12 weeks. These findings were sustained for up to 24 weeks after the last dose. “We are pleased to share data supporting the potential for a differentiated product profile for verekitug, the only known antagonist in clinical development targeting the TSLP receptor,” said Aaron Deykin, M.D., Upstream Bio's Chief Medical Officer and Head of R&D. “TSLP receptor inhibition with verekitug has led to rapid, substantial and sustained reductions in disease-related biomarkers that are known to predict a reduction in exacerbations, which are clinically meaningful to patients with asthma. The data and related PK/PD modeling suggest significant potency and support our evaluation of dosing intervals of every 12 or 24 weeks in our ongoing Phase 2 VALIANT clinical trial in severe asthma. We look forward to further understanding the potential of verekitug to improve clinical outcomes and enhance patient care.” Oral data presentation details are as follows: Date and Time: September 9, 2024, 2:50 p.m. CESTPresentation Title: 32-week data from a multiple ascending dose trial with verekitug, a novel antibody to the human TSLP receptor (TSLPR), in adults with asthmaSession Title: Recent advances in biological treatments for asthma and chronic obstructive pulmonary disease A digital version of the presentation can be found on Upstream’s website. About the Phase 1b MAD Study The multiple ascending dose (MAD) study was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled adults with mild to moderate asthma and elevated blood eosinophils. Four dosing cohorts were included: 100 mg every 4 weeks, 200 mg every 4 weeks, 300 mg every 12 weeks and 25 mg single dose. Participants were observed for 32 weeks following randomization (NCT05448651). About TSLP and TSLP Receptor 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 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 potently binds to the TSLP receptor and inhibits proinflammatory signaling initiated by TSLP. Verekitug is the only known antagonist in clinical development targeting the TSLP receptor. Three Phase 1 clinical trials have been completed for verekitug across a total of 120 participants, including 32 patients with asthma. In the Phase 1 single ascending dose (SAD) and Phase 1b multiple ascending dose (MAD) clinical trials, verekitug was well tolerated, demonstrated no evidence of clinically meaningful immunogenicity, showed a predictable and consistent pharmacokinetic profile, and had high subcutaneous bioavailability. Results of the Phase 1b MAD trial 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. Verekitug is currently being evaluated in two placebo-controlled, multi-national, randomized Phase 2 clinical trials. The VALIANT trial is a Phase 2 clinical trial in an estimated 436 patients with severe asthma, in which verekitug is administered at dosing intervals of either once every 12 weeks or once every 24 weeks with a primary endpoint of annualized asthma exacerbation rate (NCT06196879). The VIBRANT trial is a Phase 2 clinical trial in approximately 70 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), in which verekitug is administered at a dosing interval of once every 12 weeks with a primary endpoint of change from baseline in nasal polyp score at week 24 (NCT06164704). About Upstream Bio Upstream Bio is a clinical-stage biotechnology company developing treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. Upstream Bio is developing verekitug, the only known antagonist currently in clinical development that targets the receptor for Thymic Stromal Lymphopoietin (TSLP). The focus of Upstream Bio is to maximize verekitug’s unique attributes to address the substantial unmet needs of patients with severe asthma and CRSwNP that are underserved by today’s standard of care. Beyond these initial indications, Upstream Bio believes verekitug has broad potential in other inflammatory diseases, and it intends to leverage verekitug’s differentiated attributes to develop it as a potential therapy for diseases where TSLP signaling has been shown to play a significant role.