NodThera Ltd.

BioAge Labs has picked brain-penetrant molecule BGE-102 as its development candidate. \n BioAge Labs has given up on its lead obesity candidate. Weeks after stopping a trial in response to phase 2 data, the biotech has jettisoned the molecule and shifted its focus to a preclinical neuroinflammation prospect.California-based BioAge raised around $200 million in an IPO in September and swiftly reminded public investors that biotechs are risky bets. Two months after going public, BioAge stopped a phase 2 trial of its oral apelin receptor agonist azelaprag. Investors fled, but the biotech left the door open, noting that it remained encouraged by preclinical and early-phase data and vowing to share updated plans in 2025.BioAge closed the door on azelaprag Tuesday, explaining that the elevated liver enzymes seen in some patients without clear dose dependence had persuaded it to call time on the program. The biotech has structurally distinct molecules in its pipeline and aims to pick a follow-up candidate this year.With the apelin program bouncing back to preclinical, BioAge’s NLRP3 inhibitor has become the biotech’s most advanced prospect. Management has picked brain-penetrant molecule BGE-102 as its development candidate and is running studies to support a filing to test the asset in humans. BioAge expects to post phase 1 single-ascending dose data on the candidate this year. NLRP3 was a hot target as the 2010s drew to a close, when Bristol Myers Squibb, Novartis and Roche—both through its mothership and Genentech subsidiary—all acquired assets. None of the deals has led to an approved NLRP3 inhibitor.BioAge is initially focused on molecules that are active in the central nervous system. NodThera, Ventyx Biosciences, Roche and Ventus Therapeutics have all worked on similar molecules, but BioAge is bullish, with CEO Kristen Fortney, Ph.D., using a Citi event last month to claim the candidates are “an order of magnitude more potent than the competition.”The biotech’s focus on the neuroinflammatory uses of NLRP3 inhibition is built on longevity data linking the protein to accelerated cognitive aging and shorter life spans. BioAge also has evidence that inhibiting the protein could suppress appetite, suggesting there is scope to expand into obesity.Investors appeared to have priced in the pivot away from azelaprag, with the stock opening flat Tuesday. BioAge’s stock has fallen more than 75% since last year’s IPO, but the biotech has the money to write a second act—the company\'s cash runway extends beyond 2029. BioAge disclosed a collaboration with Lilly ExploR&D to discover two antibodies against metabolic aging targets identified by the biotech.

The trial enrolled patients with obesity and elevated baseline C-reactive protein, a biomarker of chronic inflammatory diseases such as coronary artery disease. NodThera’s NLRP3 inhibitor has already proved its worth against Novo Nordisk’s blockbuster obesity drug in preclinical trials. Now, an early readout from a study in humans with obesity has again demonstrated the drug’s anti-inflammatory potential. The phase 1b/2a trial saw patients with obesity and elevated baseline C-reactive protein (CRP)—a biomarker of chronic inflammatory diseases such as coronary artery disease—receive either NT-0796 or placebo over 28 days. The data demonstrated a “highly statistically significant and rapid” reduction in CRP among patients who received NT-0796 compared to the placebo cohort, hitting the study’s primary endpoint. In addition, more than 75% of the NT-0796 cohort achieved a CRP reduction of 2mg/L or more—considered a threshold for reducing cardiovascular risk—compared to less than 25% of those on placebo, NodThera noted in a June 12 release. The biotech also pointed to reductions in other additional pro-inflammatory and cardiometabolic biomarkers, which it said built on its weight loss studies in mice as well as a phase 1b/2a study in patients with Parkinson’s disease. “While all subjects lost weight due to calorie restriction in both the active and placebo groups, the most pronounced placebo-adjusted reductions in body weight were among high-risk subgroups of NT-0796 dosed subjects, and, with the company’s earlier preclinical data, support the anti-obesity potential of the molecule,” NodThera said in the release. The company is now preparing to launch a 26-week phase 2 study in obesity alongside other mid-stage studies ranging from additional cardiometabolic diseases to Parkinson’s disease. Today’s readout builds on the promise demonstrated by NT-0796 in both preclinical and clinical studies so far this year. In February, the company showed that NT-0796 caused weight loss at nearly the same rate as Wegovy in mice. The results demonstrated that NLRP3 inhibitors are “uniquely positioned” over GLP-1 receptor agonists to block the initiation of cellular inflammatory responses to obesity-related damage-associated molecular patterns, researchers wrote in an article (PDF) published at the time in the Journal of Pharmacology and Experimental Therapeutics. Last month, a phase 1b/2a study showed that NT-0796 resulted in mean reductions of key pro-inflammatory biomarkers in Parkinson’s patients. NodThera President and Chief Scientific Officer Alan Watt, Ph.D., described today’s results as “an impressive data set, made all the more remarkable by being achieved within 28 days.” “In addition to the profound anti-neuroinflammatory effects in Parkinson’s disease patients demonstrated previously, the data generated in this study of NT-0796 show improvements in inflammatory and metabolic biomarkers of CV risk that go beyond that seen with antibody and peptide therapies,” Watt added in the release. “With additional reductions in body weight that should be enhanced with longer-duration dosing, NT-0796 is confirmed as a highly promising therapeutic agent for chronic inflammatory indications,” Watt said.

A Boston-based biotechnology company on Thursday said its most advanced drug showed positive effects in a clinical trial of Parkinsons disease patients, results that at least one analyst believes could help validate another, similar therapy.The company, NodThera, said that over the course of four weeks, patients given its drug experienced reductions in key biological markers tied to the inflammation and degradation of the nervous system. The drug was also safe and well tolerated, according to NodThera, with no serious adverse events observed.Specific data werent disclosed, though the trials findings will be presented Friday at a conference dedicated to Parkinsons and Alzheimers disease research. NodThera now plans to push its drug into mid-stage studies.Given that existing Parkinsons treatments primarily manage symptoms, our innovative, disease-modifying strategy presents a significant shift, aiming to stop the disease progression, said Alan Watt, the companys CEO, in a statement.Taken orally, NodTheras drug is designed to inhibit a protein complex known scientifically as an NLRP3 inflammasome. Research suggests Parkinsons is caused, at least in part, by misfolded proteins that form toxic aggregates. These aggregates are thought to then activate inflammasomes, which can lead to nerve cell damage and death.Drug hunters expect that inflammasome-blocking agents could be useful in treating a variety of diseases, from neurodegenerative ones to obesity to a common liver illness called MASH. NodThera itself is also testing its leading drug in people who are obese and at risk of cardiovascular disease.The area of research has even attracted investment from some of the worlds largest developers. Swiss pharmaceutical giant Roche bought two biotechs focused on NLRP3 biology. And in 2022, Novo Nordisk spent $70 million to license a medicine targeting NLRP3 proteins.Shares of Ventyx Biosciences, another small drugmaker developing a couple of these agents, rose nearly 15% following NodTheras disclosure. Also on Thursday, Ventyx announced it was raising $100 million through a private placement of common stock.Michael Yee, an analyst at Jefferies, wrote in a note to clients that the NodThera results are a positive for Ventyx and gives his team confidence we will see promising signals in an early-stage trial testing one of Ventyxs NLRP3 drugs in healthy volunteers. The biotech plans to release high-level results from that trial on Monday.NodTheras study represents another datapoint supporting NLRP3's role and importance ... for neuro indications and possibly obesity, Yee added.Founded in 2016 by Epidarex Capital, NodThera is now backed by a group of high-profile life sciences investors that includes 5AM Ventures, Cowen Healthcare Investments, F-Prime Capital, Novo Holdings, Sanofi Ventures and Sofinnova Partners. The company raised $40 million through a Series A round in 2018 and then $55 million two years later via a Series B financing. '