Asthma patients have many drug options, but many patients find these choices either inconvenient or inadequate for severe cases of the chronic respiratory condition. Upstream Bio is pursuing a validated immunological target with a drug it contends offers dosing and efficacy advantages over a commercialized asthma medication from AstraZeneca and Amgen, and the biotech now has $225 million in IPO cash to help build its case with clinical data.

Investors are persuaded by Upstream’s ambition, and their interest in the biotech’s new stock enabled the company to boost the deal size. After setting preliminary IPO terms of 12.5 million shares in the range of $15 to $17 each, which would have raised $200 million at the pricing midpoint, the Waltham, Massachusetts-based biotech on Thursday ended up offering 15 million shares at the top of the targeted price range. Upstream’s shares now trade on the Nasdaq under the stock symbol “UPB.” On Friday, Upstream’s first day on the public markets, the company’s stock price closed at $22, up 29.4% from the IPO price.

Severe asthma is defined as disease that is uncontrolled despite treatment with high-dose inhaled corticosteroids. It can also be asthma that requires high-dosed inhaled corticosteroids to prevent symptoms from becoming uncontrolled. Biologic drugs offer patients an alternative treatment option for cases of uncontrolled asthma. Upstream’s lead drug is verekitug, a monoclonal antibody designed to block thymic stromal lymphopoietin, or TSLP. This signaling protein plays a role in immunological disorders and it’s upstream of multiple signaling cascades involved in many immune-mediated diseases, the company said in its IPO filing.

Of the six biologic drugs currently approved for severe asthma, only the AstraZeneca and Amgen product Tezspire addresses TSLP. But while Tezspire blocks the TSLP ligand, Upstream’s drug blocks the TSLP receptor. Upstream contends its approach could offer better control of asthma symptoms. It also offers potential for less frequent dosing. The company is testing dosing every 12 weeks and every 24 weeks — a much lower dosing burden compared to once monthly injections of Tezspire.

“We believe that by reducing the frequency of dosing we can increase patient compliance with biologic treatments for severe asthma,” Upstream said in its IPO filing. “Additionally, a less frequent dose interval may appeal to patients that are not satisfied with their current treatment plan or are unwilling to take current biologics due to the treatment burden that comes with frequent dosing.”

In Phase 1b testing, Upstream reported its drug led to “rapid and complete TSLP receptor occupancy.” Results also showed reductions in biological indicators of asthma that were sustained for up to 24 weeks after the last dose. Tezspire, which won FDA approval in 2021, was not part of this study as a comparator. But Upstream said verekitug’s results show it was about 300-fold more potent than the AstraZeneca and Amgen product based on published data for that drug. The Phase 1b results were presented in May during the American Thoracic Society International Conference.

A Phase 2 test of verekitug in severe asthma began this past March; preliminary data are expected in the second half of 2026. Upstream’s approach to blocking TSLP has potential in other immunological conditions. A Phase 2 test in chronic rhinosinusitis with nasal polyps is expected to yield data in the second half of 2025. A separate mid-stage trial in chronic obstructive pulmonary disease (COPD) is expected to begin in the second half of next year.

Verekitug was discovered by Astellas Pharma, which advanced the drug candidate to Phase 1 testing. In 2021, months after Upstream formed, the young company acquired the Astellas asset for $81.1 million, according to the filing. There are no future payments owed to the Japanese pharma company.

Upstream had raised $400 million from investors prior to the IPO, according to the filing. The company’s most recent financing was a $150 million Series B round announced in June and led by Enavate Sciences and Venrock Healthcare Capital Partners. Orbimed is Upstream’s largest shareholder with a 9.9% post-IPO stake, the filing shows. As of the end of June, the company reported its cash position was $235.8 million.

Now that Upstream is public, the company plans to spend $150 million to continue the ongoing Phase 2 test of its lead program in severe asthma and advance it into Phase 3. About $40 million is budgeted for completing a Phase 2 test of the molecule in chronic rhinosinusitis with nasal polyps and starting a Phase 3 test in this indication. Another $50 million is set aside for costs associated with verekitug drug substance, including manufacturing. The company said it expects its capital will be sufficient to fund operations through mid-2027.

CAMP4 Therapeutics Corrals $75M for Trials With a New Kind of RNA Therapy

CAMP4 Therapeutics, a company named for the final camp before the summit of Mount Everest, has $75 million in IPO cash to continue development of treatments for haploinsufficiencies, disorders in which dysfunction in one copy of a gene leads to abnormally low levels of a key protein. The Cambridge, Massachusetts-based biotech aims to treat disease by targeting regulatory RNA, or regRNA, a type of RNA that regulates gene expression.

The CAMP4 drugs are antisense oligonucleotides that bind to regRNA and get it to dial up gene expression. In a 2021 interview, CAMP4 CEO Josh Mandel-Brehm compared the approach to using a rheostat to adjust an electrical current. The company’s drugs, called RNA actuators, amplify gene expression in a controllable way, he said. Metabolic and central nervous system haploinsufficiencies are the company’s initial areas of focus.

Lead program CMP-CPS-001 is in development for urea cycle disorders, inherited metabolic diseases that render the body unable to properly convert ammonia into urea. CAMP4’s drug is designed to amplify expression of an enzyme that catalyzes the first step of the urea cycle. In preclinical research, results showed a lowering of ammonia levels to normal ranges. A Phase 1 test is underway in healthy volunteers. Data from the single dose ascending portion of the trial are expected in the first quarter of 2025; the multiple ascending dose portion is expected to have data in the second half of next year. The next program in the pipeline is a preclinical treatment for SYNGAP1-related disorders, neurodevelopmental conditions caused by pathogenic variants in the SYNGAP1 gene. This haploinsufficiency leads to SYNGAP levels up to 50% below the normal range.

CAMP4 had raised $183.3 million prior to its IPO. The company’s most recent financing was a $100 million Series B round in 2022 led by Enavate Sciences. Enavate is CAMP4’s largest shareholder with a 13.7% post-IPO stake, followed by 5AM Ventures with an 11.4% stake, the filing shows.

As of the end of the second quarter of this year, CAMP4 reported a $12.6 million cash position. With the IPO proceeds, the company plans to spend $26 million to complete the Phase 1 test of its lead drug candidate for urea cycle disorders. About $18 million is set aside for continuing preclinical development of the SYNGAP1 program. Another $10 million is budgeted for expanding CAMP4’s platform technology and for development of other programs in the preclinical and discovery stages.

CAMP4 was able to raise the money it needs for its plans, but it had to significantly cut its IPO price to do so. In preliminary IPO terms set earlier this week, CAMP4 planned to offer 5 million shares in the range of $14 and $16 each, which would have raised $75 million at the pricing midpoint. CAMP4 reached its $75 million goal by offering 6.82 million shares priced at $11 apiece. Those shares are trading on the Nasdaq under the stock symbol “CAMP.”

CeriBell Upsizes IPO to Support a Commercialized EEG Tech Employing AI

Medical technology company CeriBell raised $180.3 million to bolster commercialization efforts for its FDA-cleared electroencephalography (EEG) technology. The Ceribell System uses artificial intelligence to aid in the detection and management of seizures. The hardware is a disposable headband and a pocket-sized recorder that captures and wirelessly transmits EEG signals. An AI-powered seizure detection algorithm continuously monitors the patient’s EEG signal to detect seizures.

Ceribell System, which is used in intensive care units and emergency departments, commercially launched in 2018. Sunnyvale, California-based CeriBell has two sources of recurring revenue: sales of the disposable headbands and a monthly subscription fee charged to the hospital customers that use the company’s technology. In 2023, CeriBell reported $45.2 million in total revenue, a 74% increase compared to the prior year. In the first half of this year, revenue was $29.7 million, a 45% increase compared to the same period in 2023. As of the end of September, CeriBell reported its cash position was $14 million. With the IPO proceeds, CeriBell plans to use $90 million for sales and marketing and $20 million for research and product development.

CeriBell was able to upsize its IPO. In preliminary financial terms set earlier this week, the company estimated it would raise $88.9 million. The company revised those terms early Thursday, aiming to offer 6.7 million shares in the range of $16 to $17 each, which would have raised $174.9 million at the pricing midpoint. When the company finally priced its IPO late Thursday, it ended up offering 10.6 million shares priced at the top of the range. CeriBell’s shares trade on the Nasdaq under the stock symbol “CBLL.”

Image: Jackie Niam, Getty Images

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