Basmisanil

Newleos Therapeutics is named after its mission to create a new dawn or \"eos\" for patients with mental health conditions.\n Newleos Therapeutics is making its debut with $93.5 million aimed at developing safer and more effective neuroscience treatments with several clinical programs from Swiss major Roche in hand.The oversubscribed series A financing was led by Goldman Sachs Alternatives with participation from Longwood Fund, Novo Holdings, DCVC Bio and Arkin Bio Capital, according to a Feb. 13 release.Named after its mission to create a new dawn or \"eos\" for patients with mental health conditions, Newleos was co-founded by the VC Longwood Fund, scientist and biotech exec Federico Bolognani, M.D., Ph.D., and Longwood Fund senior advisor William Martin, Ph.D. Bolognani currently serves as Newleos\' chief medical officer and Martin as the biotech\'s start-up chief development officer.The Boston-based biotech has emerged with a clutch of oral small molecules targeting novel mechanisms across several neuropsychiatry indications, according to the release.Newleos paid Roche an undisclosed upfront sum for the programs and is offering the Big Pharma success-based milestones and royalties in exchange for worldwide rights to the assets. The biotech will use its series A funds to run proof-of-concept clinical trials across the programs, founding Newleos CEO and Longwood Fund Executive Partner David Donabedian, Ph.D., said in the release. The new company’s lead clinical program, known as NTX-1955 and previously RO7308480, is a potentially first-in-class GABAA-γ1 selective positive allosteric modulator (PAM). Newleos is testing the candidate out as a treatment for generalized anxiety disorder, with hopes that the differentiated mechanism of action will eliminate the side effects seen with currently approved treatments.Roche had examined NTX-1955 in several phase 1 trials, including single and multiple ascending dose studies, drug-drug interaction and receptor occupancy studies. The trials found NTX-1955 to be safe, well tolerated, brain penetrant and selective to GABAA-γ1, according to Newleos.Roche had run a European phase 1 trial for the candidate in 2023 among healthy participants. The pharma had been aiming to see whether the small molecule could have been a treatment for social anxiety disorder. Newleos has also picked up NTX-1472—known as RO6953958 at Roche’s Genentech—a V1a antagonist that the biotech plans to run proof-of concept studies for in social anxiety disorder. Previously, Roche’s subsidiary tested the candidate out in a phase 1 study of healthy men and had been interested in potentially using the asset for autism spectrum disorder, according to clinical trial information posted by Genentech.The Boston biotech has also secured Roche’s ralmitaront, now to be known as NTX-2001, a midstage asset that Roche culled back in October 2023. The pharma terminated a phase 2 schizophrenia trial of the candidate earlier in the year after an interim analysis found it was unlikely to meet the primary endpoint, which measured change from baseline in negative symptoms at Week 12. Roche had also discontinued another trial assessing the program among patients with acute exacerbation of schizophrenia or schizoaffective disorder the year before.NTX-2001 is a TAAR1 partial agonist, and Newleos plans on examining its potential in substance use disorders.Lastly, Newleos nabbed NTX-1511—previously dubbed basmisanil—which is designed to be a highly selective negative allosteric modulator (NAM) of the alpha-5 subunit of the GABAA receptor. The biotech believes the asset has the potential to address cognitive impairment in rare neurodevelopmental indications.    Previously, Roche tried out the candidate in ischemic stroke and schizophrenia from 2016 to 2019 to no avail. Then, in 2022, the pharma launched a phase 2 trial for the program in a developmental disorder, but removed the asset from its pipeline in 2024.“A majority of anxiety patients fail to respond to first line therapy with SSRIs and SNRIs, and benzodiazepines are not recommended for long term use due to side effects such as sedation, potential for misuse and dependence and cognitive decline,” Christoph Westphal, M.D., Ph.D., founding executive chair for Newleos and founding partner of the Longwood Fund, said in the release. “Newleos’ portfolio of clinical stage candidates provides an exciting opportunity to advance truly differentiated medicines for some of the most prevalent indications like anxiety and substance use disorders.” This story was updated at 9 a.m. ET on Feb. 13 to include new information about Newleos\' co-founders.

Roche’s clear-out was accompanied by an influx of other assets. Roche has removed eight phase 1 and 2 oncology and neurology candidates from its pipeline as part of a set of “trade-offs” intended to “increase the overall portfolio value and speed up development.” In the fourth quarter (PDF), Roche removed eight drug candidates and replaced them with eight different prospects, shifting the balance of its pipeline away from neurology and, to a lesser extent, oncology and toward immunology, cardiovascular and metabolism in the process. The number of neurology prospects fell from 18 to 12, although one of those was moved to another part of the pipeline. CEO Thomas Schinecker said the the resources will be shifted "to projects we want to accelerate." He also foreshadowed similar pipeline cuts to come in the first quarter during a fourth quarter earnings call Thursday.  Basmisanil is one of the candidates Roche is kicking to the curb. The drugmaker trialed the GABAA α5 receptor negative allosteric modulator in ischemic stroke and schizophrenia patients from 2016 to 2019. The discovery of an EEG biomarker of dup15q, a developmental disorder, spurred interest in treating the syndrome by reducing GABA activity in the brain and led Roche to start enrolling patients in a phase 2 trial in 2022. ClinicalTrials.gov lists the study as recruiting, but Roche removed the asset from its pipeline.  Roche also axed balovaptan, a small-molecule vasopressin V1A receptor antagonist that previously made it to phase 3 in autism spectrum disorder only to fail to move the needle. The drugmaker tried again in the aftermath of the failure, kicking off a phase 2 study in post-traumatic stress disorder. Roche finished that trial last year and promptly removed balovaptan from its pipeline.  News of the other neurology changes preceded the fourth-quarter update. AC Immune said Roche had returned the Alzheimer’s disease prospects crenezumab and semorinemab last month, and details of the decision to drop Angelman syndrome candidate rugonersen emerged via the patient community last year.  On the oncology side, Roche removed three phase 1 candidates from the pipeline. The drugmaker dealt a second blow to the hopes of treating solid tumors by targeting FAP. Having already stopped studying a FAP-IL-2v candidate, Roche removed the solid tumor FAP-CD40 prospect RG6189 from its pipeline in the fourth quarter. A phase 1b trial of a FAP-4-1BBL candidate, RG7827, is continuing.   The other two axed oncology assets are the EGFRvIIIxCD3 bispecific antibody RG6156, which Roche was studying in brain cancer, and another bispecific designed to bind to HLA-G on tumor cells and CD3 on T cells.  Roche’s clear-out was accompanied by an influx of other assets, including candidates acquired through the takeovers of Carmot Therapeutics and Telavant. A longer-term bet delivered a clinical candidate, too, with Roche moving a covalent inhibitor of WRN, the synthetic lethal target at the heart of a $135 million deal with Vividion Therapeutics, into phase 1.