AT2R

Boehringer’s nerandomilast is a preferential inhibitor of phosphodiesterase 4B (PDE4B). Image credit: Tada Images / Shutterstock. Boehringer Ingelheim is seeking regulatory approval for nerandomilast after a Phase III trial in idiopathic pulmonary fibrosis (IPF) met its primary endpoint. Boehringer confirmed the Phase III FIBRONEER-IPF trial (NCT05321069) met its primary endpoint of improving the forced vital capacity, a measure of lung function after 52 weeks. The company plans to present full efficacy and safety data from the study in the first half of 2025. Boehringer was quick to tout that nerandomilast’s Phase III trial was the first IPF late-stage trial in a decade to meet its primary endpoint. This is not the first time Boehringer has found success in the space. Its tyrosine kinase inhibitor (TKI) Ofev (nintedanib) was approved by the US Food and Drug Administration (FDA) to treat IPF in 2014. It has since been approved in the US for interstitial lung disease associated with systemic sclerosis or scleroderma (SSc-ILD) and chronic interstitial lung disease. Ofev has also raked in record profits for Boehringer , last year the therapy generated €3.5bn ($3.89bn) in global sales. The Phase III FIBRONEER-IPF trial enrolled 1,177 patients with IPF randomised to receive either nerandomilast or placebo twice daily. The study’s secondary endpoint is time to the first occurrence of acute IPF exacerbation, first hospitalisation for respiratory cause, or death. See Also: Bicara Therapeutics closes $362m IPO in flurry of biotech listing activity MaxCyte and Kamau Therapeutics sign platform license agreement Nerandomilast is a preferential inhibitor of phosphodiesterase 4B (PDE4B). It received a breakthrough therapy designation from the US FDA for the treatment of IPF in 2022. Boehringer is also investigating nerandomilast in patients with progressive fibrosing interstitial lung diseases in a Phase III FIBRONEER-ILD trial (NCT05321082), which is due for completion by the end of the year. IPF has a high unmet need as there are only two US FDA-approved medications, Ofev and Roche’s Esbriet (pirfenidone). Whilst Roche’s TGF-beta synthesis inhibitor also secured FDA approval in 2014, it has seen its profits erode due to the introduction of generics . The drug earned SFr718m ($752m) in sales in 2022, which dropped to CHF202m ($239m) in sales last year, as per Roche’s financials. The majority of other therapies in development for IPF are in Phase II clinical trials. In May, Vicore Pharma’s Phase IIa trial of angiotensin II type 2 receptor (AT2R) agonist buloxibutid in IPF met both its primary and secondary endpoints. Bridge Biotherapeutics’ Phase II trial evaluating its autotoxin inhibitor , BBT-877 in IPF is expected to report topline data in the first half of 2025.

Founded nearly a decade ago to develop GPCR-targeting drugs, Confo Therapeutics has found itself in a prime position as the industry-wide weight-loss craze — driven by GPCR family member, GLP-1— reaches new heights. The Belgium-based biotech raised €60 million ($65.1 million) in a series B financing Friday to advance its GPR75-targeting obesity candidate along with three others in the endocrine and metabolic disease space. Confo isn’t sharing much about the other programmes it’s progressing, but the funds will advance two through Phase I testing, and help another pair ready for IND. According to the company’s website, it has a mix of antibodies and small molecules in development for conditions such as hyperparathyroidism, hyperinsulinemia, and fibrotic diseases.The firm also has an AT2R-targeting peripheral pain candidate in a Phase I trial. Eli Lilly paid $40 million upfront last year to gain rights to that therapy, and is on the hook for $590 million more in milestones.GPCR stabilisationWhile Confo’s pipeline may seem wide-reaching, that’s only because GPCRs “play a role in almost any disease you can think of,” CEO Cedric Ververken told FirstWord, naming asthma and diabetes, as well as central nervous system and cardiovascular disorders. Despite the strong scientific rationale behind modulating GPCRs for various diseases, there are hundreds of receptors that have yet to be successfully targeted. That’s due to two factors, Ververken explained: the proteins are deeply embedded in the cell membrane, and they’re conformationally unstable, making them difficult to study. That’s where the ConfoBodies platform comes in. The company has developed a suite of tool antibodies to stabilise GPCR proteins in their therapeutically relevant conformation, enabling increased screening sensitivity for drug discovery.The technology is so powerful, Ververken said, that Confo can pick up on fragments, which are “really tiny chemical starting points” that wouldn’t be detected in a normal signalling assay. “Starting from something that small allows us to build up these drugs in a very efficient way without built-in toxicophores or lipophilic parts,” he added. “We can really maintain favourable drug-like properties from the start.” Plus, Confo isn’t limited to small molecules. The company also boasts a therapeutic antibody generation platform geared specifically towards agonists, “which is quite a unique feat in the industry,” Ververken said.There are three GPCR-targeted antibodies on the market, but none are agonists. Confo’s agonist antibody capabilities are part of what’s helped the firm to attract deals with Regeneron and AbCellera, he added. All systems go on obesityFor its internal pipeline, Confo is initially focusing on endocrine and metabolic diseases because there’s a wealth of biologically relevant GPCRs in that space — with GLP-1 as a prime example. Plus, the pharmacology of these particular receptors is well-established, making therapeutic activity easier to confirm in Phase I healthy volunteer studies, Ververken said. From there, it’s a straightforward path to clinical proof-of-concept.The space also has a healthy mix of rare disease opportunities that can be tackled by a small biotech, as well as big indications like obesity that are attractive to pharma. “It allows us to build a pipeline towards an IPO, but it also allows us to work on projects that could potentially drive an M&A deal at some point,” Ververken commented. Obesity is where Confo is planning on allocating the majority of its resources as it races to be first in the clinic with its GPR75 agonist, he added. The target was first linked to obesity in 2021 when a genetic study showed that individuals with a loss-of-function mutation in the gene had a lower risk of obesity and improvements in certain metabolic measures that suggested the protein played a role in muscle-mass preservation.  That muscle benefit falls squarely within the next-generation weight-loss drug wish list, along with improved tolerability. For more, see Spotlight On: How obesity drug developers aim to combat muscle loss.Ververken said that several phamas looking for new obesity assets are interested in GPR75, and other companies are working to develop their own agonists. “But we intend to lead the race,” he asserted.

STOCKHOLM, SE / ACCESSWIRE / May 31, 2024 / Vicore Pharma Holding (STO:VICO) Stockholm, May 31, 2024 - Vicore Pharma Holding AB (STO: VICO) ("Vicore") announced today that the number of Vicore shares and votes has increased following the exercise of warrants with subsequent delivery of shares to a participant in the incentive program Board LTIP 2023. The shares were issued through the exercise of 11,025 share rights, which are entitled to an equal number of shares. Through the share awards, the number of outstanding shares and votes increased by 11,025 and the share capital by 5,512.499947 SEK. As of today, the total number of registered shares and votes amount to 111,734,004. Furthermore, the registered share capital amounts to 55,867,001.457610 SEK. About Vicore Pharma Holding AB (a clinical-stage biopharmaceutical company) Vicore is an innovative clinical-stage pharmaceutical company unlocking the potential of a new class of drugs with disease-modifying potential. The company is establishing a portfolio in respiratory diseases, including idiopathic pulmonary fibrosis (IPF). Buloxibutid (C21) is a first-in-class orally available small molecule angiotensin II type 2 receptor agonist (ATRAG) recently completing a phase 2a study in IPF. Almee™ (an investigational medical device in clinical development) is a digital therapeutic based on cognitive behavioral therapy created to address the psychological impact of living with pulmonary fibrosis. Almee has received Breakthrough Device Designation from the FDA, reflecting its potential to have transformative impact. Using its unique expertise in ATRAG chemistry and biology, Vicore is further fueling its pipeline with several new therapies across additional potential indications. The company's shares (VICO) are listed on Nasdaq Stockholm's main market. For more information, see This information is information that Vicore Pharma Holding is obliged to make public pursuant to the Financial Instruments Trading Act. The information was submitted for publication at 2024-05-31 09:00 CEST. Attachments Increase of number of shares and votes in Vicore Pharma SOURCE: Vicore Pharma Holding View the original press release on accesswire.com