A Phase III Multicenter Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Adult Patients With Relapsing Multiple Sclerosis

Start Date28 Feb 2023

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Fenebrutinib

100 Translational Medicine associated with Fenebrutinib

100 Patents (Medical) associated with Fenebrutinib

Literatures (Medical) associated with Fenebrutinib

01 May 2025·Clinical and Translational Allergy

Biological and target synthetic treatments for chronic spontaneous urticaria: A systematic review and network meta‐analysis

Article

Author: Song, Xiaoting ; Peng, Chengyue ; Zhang, Peixin ; Zheng, Yaqi ; Zhang, Litao ; Huang, Xiaojie ; Tan, Yen ; Zhao, Zuotao ; Liao, Shuanglu

Abstract:

Background:

Most biological and synthetic target‐specific drugs for antihistamine‐refractory chronic spontaneous urticaria (CSU) have not been compared head‐to‐head. This systematic review and network meta‐analysis evaluated their relative efficacy and safety.

Methods:

Searches were conducted on PubMed, Embase, Web of Science and Cochrane library databases to March 25, 2024 for randomized trials. A random‐effects model was used to calculate the network estimates reported as mean differences (MD) and odds ratios (OR) with corresponding 95% CIs. Main outcomes included the weekly urticaria activity score (UAS7), adverse events (AEs) and serious adverse events (SAEs).

Results:

23 randomized clinical trials with 6933 participants that compared 26 different interventions or dosages and placebos were included. Omalizumab 300 mg [MD −10.07, 95% CI (−11.35; −8.82)] continues to demonstrate superior efficacy compared with placebo. Remibrutinib, at doses of 35 mg once daily [MD −7.80, 95% CI (−12.76; −2.51)], 25 mg twice daily [MD −7.69, 95% CI (−9.85; −5.76)], and 10 mg twice daily [MD −7.61, 95% CI (−12.59; −2.47)], had the best overall performance for efficacy and safety. Dupilumab, fenebrutinib, and rilzabrutinib also showed greater efficacy than placebo. The results were similar for the proportion of patients who achieved UAS7 ≤ 6 or UAS7 = 0. No significant differences were found among all treatment comparisons for AEs and SAEs.

Conclusion:

The findings of this study indicate that the biological agent omalizumab 300 mg and the oral small molecule remibrutinib at doses of 35 mg, 25 mg, or 10 mg are recommended for patients with antihistamine‐refractory CSU.

Trial Registration:

PROSPERO: CRD42024516289

01 May 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Next generation Bruton's tyrosine kinase inhibitors – characterization of in vitro potency and selectivity

Article

Author: Angst, Daniela ; Cenni, Bruno ; Pulz, Robert

Bruton's tyrosine kinase (BTK) mediates B cell receptor and Fc receptor signaling and is a key regulator of autoimmunity and allergy. A series of novel BTK inhibitors (BTKi) are currently in development for non-oncologic indications with covalent-irreversible (remibrutinib, evobrutinib, tolebrutinib, orelabrutinib), covalent-reversible (rilzabrutinib), and non-covalent reversible (fenebrutinib) binding modes. This study characterizes their in vitro potency and selectivity profiles under the same conditions to minimize assay differences across the different binding modes. Covalent BTKi showed human in vitro blood BTK binding in a time- and concentration-dependent manner with remibrutinib being the most potent and fastest in onset of action. Cellular BTK pathway inhibition was determined in human blood B cells and basophils, and for covalent BTKi correlated well with BTK binding. In contrast to the covalent-irreversible remibrutinib, the non-covalent reversible fenebrutinib showed rapid loss of cellular BTK inhibition after washout. Kinase selectivity was assessed in a binding screen across the human kinome, followed by quantification of binding affinities for a selection of kinases. BTKi ranked in their selectivity as follows (most selective to least): remibrutinib, fenebrutinib, evobrutinib, orelabrutinib, rilzabrutinib and tolebrutinib. These data suggest that next generation BTKi show important differences in their in vitro target binding and selectivity when compared under the same conditions.

11 Apr 2025·ACS Pharmacology & Translational Science

Comprehensive Characterization of Bruton’s Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures

Review

Author: Servant, Nicole B. ; King, Alastair J. ; Jahic, Mirza ; Darragh, Antonia C. ; Lipner, Justin H. ; Hanna, Andrew M.

Uncovering a drug's mechanism of action and possible adverse effects are critical components in drug discovery and development. Moreover, it provides evidence for why some drugs prove more effective than others and how to design better drugs altogether. Here, we demonstrate the utility of a high-throughput in vitro screening platform along with a comprehensive panel to aid in the characterization of 15 Bruton's tyrosine kinase (BTK) inhibitors that are either approved by the FDA or presently under clinical evaluation. To compare the potency of these drugs, we measured the binding affinity of each to wild-type BTK as well as a clinically relevant resistance mutant of BTK (BTK C481S). In doing so, we discovered a considerable difference in the selectivity and potency of these BTK inhibitors to the wild-type and mutant proteins. Some of this potentially contributes to the adverse effects experienced by patients undergoing therapy using these drugs. Overall, noncovalent BTK inhibitors showed stronger potency for both the wild-type and mutant BTK when compared with that of covalent inhibitors, with the majority demonstrating a higher specificity and less off-target modulation. Additionally, we compared biological outcomes for four of these inhibitors in human cell-based models. As expected, we found different phenotypic profiles for each inhibitor. However, the two noncovalent inhibitors had fewer off-target biological effects when compared with the two covalent inhibitors. This and similar in-depth preclinical characterization of drug candidates can provide critical insights into the efficacy and mechanism of action of a compound that may affect its safety in a clinical setting.

News (Medical) associated with Fenebrutinib

30 May 2025

·www.fiercebiotech.com

Roche links BTK inhibitor to low relapse rate across 96-week multiple sclerosis trial

One patient on Roche’s fenebrutinib had an asymptomatic increase in a liver enzyme.\n Roche has shared long-term phase 2 data on its BTK inhibitor fenebrutinib in relapsing multiple sclerosis (MS), providing evidence of durability over 96 weeks to build out its case ahead of the release of pivotal trial results.BTK inhibitors have struggled in relapsing MS, with Merck KGaA axing its candidate after chalking up failures in two phase 3 trials in the setting. Meanwhile, Sanofi\'s tolebrutinib failed both of its phase 3 relapsing MS trials, although the blow was softened somewhat by a win in another form of the disease. As rivals have fallen away, Roche has continued to work toward readouts from two phase 3 trials in relapsing MS.The first data from Roche’s phase 3 program, which also includes a study in primary progressive MS, are due at the end of the year. Ahead of the readouts, Roche provided a fresh cut of data from the phase 2 trial that supported its decision to run pivotal studies in relapsing MS.Patients who took fenebrutinib for up to 96 weeks had an annualized relapse rate of 0.06. Roche saw no disability progression, as measured by the Expanded Disability Status Scale (EDSS), in the open-label extension. No active brain lesions were detected. For comparison, Sanofi reported (PDF) an annualized relapse rate of 0.17 at Week 72 of its phase 2 tolebrutinib trial in relapsing MS, with a rate of 0.20 at Week 120. Sanofi said mean EDSS remained stable to Week 120. Roche said that one patient on fenebrutinib had an asymptomatic increase in a liver enzyme after 16 weeks on the BTK inhibitor, with the case resolving after the patient stopped treatment. The FDA put a partial hold on Roche’s phase 3 relapsing MS trials in 2023 over two cases of elevated enzymes and bilirubin that suggested drug-induced liver injuries. Similar adverse events have been seen on other BTK inhibitors. Despite the adverse events, Roche has continued to make the case that fenebrutinib has advantages over other BTK inhibitors. The molecule is noncovalent and, Roche claims, more potent and selective. Teresa Graham, CEO of Roche’s pharma business, used the company’s first-quarter earnings call in April to outline why fenebrutinib could succeed where rival molecules have struggled. “We do believe that we just, frankly, have a better BTK and one that we were able to bring forward into phase 3s at what we believe to be the most appropriate dose,” Graham said. “I think that\'s the other thing that has potentially impacted some other trials, is they just weren\'t able to get to the level of dosing that they needed. We believe we\'ve gotten to the level of dose that we need.”

Phase 2Clinical ResultPhase 3Clinical Trial Failure

30 May 2025

·pipelinereview.com

Genentech’s Fenebrutinib Maintains Near-Complete Suppression of Disease Activity and Disability Progression for up to Two Years in People With Relapsing Multiple Sclerosis

– Patients on fenebrutinib had low relapse rates with data showing no active brain lesions or disability progression after nearly two years of treatment – – Phase III studies for fenebrutinib in relapsing and primary progressive multiple sclerosis are expected to start reading out at year end – SOUTH SAN FRANCISCO, CA, USA I May 30, 2025 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today new, 96-week data for fenebrutinib demonstrating that patients with relapsing multiple sclerosis (RMS) maintained no disability progression and low levels of disease activity for up to two years. The latest results for this investigational Bruton’s tyrosine kinase (BTK) inhibitor from the Phase II FENopta open-label extension (OLE) study were presented at the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting in Phoenix, Arizona. “These data show that patients treated with fenebrutinib experienced an annualized relapse rate equal to one relapse every 17 years and no observed disability progression up to two years,’’ said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Fenebrutinib is potent, highly selective and the only reversible BTK inhibitor currently in Phase III trials for multiple sclerosis, and we look forward to seeing the first of those results later this year.” Ninety-nine patients entered the OLE and 93 remained in the OLE after 96 weeks. During the OLE period, patients treated with fenebrutinib for up to 96 weeks had a low annualized relapse rate (ARR) of 0.06, and during this time there was no disability progression, as measured by the Expanded Disability Status Scale (EDSS). MRI scans showed that fenebrutinib treatment suppressed disease activity in the brain. At 96 weeks zero new T1 gadolinium-enhancing (T1-Gd+) lesions, which are markers of active inflammation, were detected. In the treatment group that switched from placebo to fenebrutinib in the OLE, the annualized rate of new or enlarging T2 lesions, which represent chronic disease burden, decreased from 6.72 at the end of the 12 week double-blind period to 0.34 by 96 weeks. The safety profile of fenebrutinib in the OLE was consistent with previously reported data, with no new safety concerns identified at 96 weeks. The most common adverse events (AEs) in ≥5% of patients were COVID-19 (10%), urinary tract infection (10%), pharyngitis (6%) and respiratory tract infection (5%). Serious AEs occurred in two patients (2%). During the OLE, one patient experienced asymptomatic alanine aminotransferase elevation at OLE week 4, after 16 weeks on treatment, which resolved with treatment discontinuation. Three Phase III clinical trials are ongoing, including the FENhance 1 and 2 trials in RMS and the FENtrepid trial in primary progressive multiple sclerosis (PPMS). The first data from these studies, which will characterize the effects of fenebrutinib on disease progression across the multiple sclerosis spectrum, are expected at the end of 2025. About fenebrutinib Fenebrutinib is an investigational oral, reversible and non-covalent Bruton’s tyrosine kinase (BTK) inhibitor that blocks the function of BTK. BTK, also known as tyrosine-protein kinase BTK, is an enzyme that regulates B-cell development and activation and is also involved in the activation of innate immune system myeloid lineage cells, such as macrophages and microglia. Preclinical data have shown fenebrutinib to be potent and highly selective, and it is the only reversible BTK inhibitor currently in Phase III trials for multiple sclerosis. Fenebrutinib has been shown to be 130 times more selective for BTK vs. other kinases. Fenebrutinib is a dual inhibitor of both B-cell and microglia activation. This dual inhibition may be able to reduce both multiple sclerosis disease activity and disability progression, thereby potentially addressing the key unmet medical need of disability progression in people living with multiple sclerosis. The fenebrutinib Phase III program includes two identical trials in relapsing multiple sclerosis (RMS) (FENhance 1 & 2) with active comparator teriflunomide and the only trial in primary progressive multiple sclerosis (PPMS) (FENtrepid) in which a BTK inhibitor is being evaluated against Ocrevus. To date, more than 2,700 patients and healthy volunteers have been treated with fenebrutinib in Phase I, II and III clinical programs across multiple diseases, including multiple sclerosis and other autoimmune disorders. About the FENopta study The FENopta study was a global Phase II, randomized, double-blind, placebo-controlled 12-week study to investigate the efficacy, safety and pharmacokinetics of fenebrutinib in 109 adults aged 18-55 years with relapsing multiple sclerosis (RMS). The primary endpoint was the total number of new T1 gadolinium-enhancing (T1-Gd+) lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. Secondary endpoints included the number of new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks, and the proportion of patients free from any new T1-Gd+ lesions and new or enlarging T2-weighted lesions as measured by MRI scans of the brain at 4, 8 and 12 weeks. The goal of the FENopta study was to characterize the effect of fenebrutinib on MRI and soluble biomarkers of disease activity and progression, and it included an optional substudy to measure cerebrospinal fluid fenebrutinib levels and biomarkers of neuronal injury. Data from the 12-week study showed that fenebrutinib is central nervous system (CNS) penetrant (crosses the blood-brain barrier) and has the potential to impact mechanisms underlying chronic progressive disease biology in multiple sclerosis patients. Fenebrutinib significantly reduced new T1-Gd+ lesions and new/enlarging T2 lesions compared to placebo. The safety profile of fenebrutinib was consistent with previous and ongoing fenebrutinib clinical trials and there were no new safety concerns identified. Patients who completed the FENopta study were given the option to take part in an open-label extension (OLE) study, in which all patients receive fenebrutinib up to 192 weeks. About multiple sclerosis Multiple sclerosis (MS) is a chronic disease that affects more than 2.9 million people worldwide. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the central nervous system (brain, spinal cord and optic nerves), causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of acquired non-traumatic disability in younger adults. People with all forms of MS experience disease progression – permanent loss of nerve cells in the central nervous system – from the beginning of their disease even if their symptoms aren’t apparent or don’t appear to be getting worse. Delays in diagnosis and treatment can negatively impact people with MS, in terms of their physical and mental health, and contribute to the negative financial impact on the individual and society. An important goal of treating MS is to slow, stop and ideally prevent progression as early as possible. Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85% of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with MS are diagnosed with the primary progressive form of the disease. Until the FDA approval of Ocrevus intravenous (IV) infusion, there had been no FDA-approved treatments for PPMS and Ocrevus IV and Ocrevus Zunovo are the only approved treatments for PPMS. About Genentech in neuroscience Neuroscience is a major focus of research and development at Genentech and Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, stroke, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Genentech Access Solutions Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http:// www.gene.com . Please see additional Important Safety Information throughout and click here for full Prescribing Information and Medication Guide for Ocrevus. Please see additional Important Safety Information throughout and click here for full Prescribing Information and Medication Guide for Ocrevus Zunovo. SOURCE: Genentech

Clinical ResultPhase 2Phase 3Drug Approval

30 May 2025

·firstwordpharma.com

Two-year data for Roche's MS hopeful sets the stage for Phase III readout

Roche shared long-term Phase II data for its experimental multiple sclerosis (MS) drug on Friday, adding to fenebrutinib's momentum ahead of a hotly anticipated late-stage readout expected by year-end.While BTK inhibitors were once seen as a promising treatment for MS given their oral dosing, analysts have since adopted a much more sceptical view of the class after several candidates failed to demonstrate efficacy in the clinic. However, Roche thinks fenebrutinib can succeed where others have failed thanks to its unique profile as a non-covalent reversible BTK inhibitor — and thus far, early data for the candidate, including Friday's readout from the Phase II FENopta open-label extension study, seem to support the Swiss pharma's argument. Fenebrutinib's potential to breathe life back into BTK inhibitors for MS earned it a place on FirstWord's list of drugs that will shape 2025, and the upcoming Phase III data release was named as one of the most important clinical readouts to watch for this year. For more analysis on the candidate, see Spotlight On: Roche keeps faith with fenebrutinib.Disease progression haltedAt the Consortium of Multiple Sclerosis Centers (CMSC) meeting Friday, Roche reported data from 93 patients with relapsing MS who remained in the FENopta study for at least 96 weeks. Patients treated with fenebrutinib had an annualised relapse rate (ARR) of 0.06 and showed no signs of disability progression, as measured by the Expanded Disability Status Scale (EDSS).According to the results of MRI scans, fenebrutinib suppressed disease activity in the brain. At the 96-week mark, patients who received the BTK inhibitor did not have any new T1 gadolinium-enhancing lesions, which are markers of active inflammation. Roche said the open-label extension study didn't identify any new safety concerns, with fenebrutinib's profile consistent with earlier readouts. Serious adverse events occurred in two patients, including one case of asymptomatic alanine aminotransferase elevation, which resolved with treatment discontinuation.Three Phase III studies of fenebrutinib are ongoing — the FENhance 1 and 2 trials in relapsing MS, and the FENtrepid trial in primary progressive MS. Roche said the first data from these studies are expected at the end of 2025.

Phase 2Clinical ResultPhase 3

100 Deals associated with Fenebrutinib

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple sclerosis relapse	Phase 3	United States	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	China	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Argentina	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Dominican Republic	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Finland	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Georgia	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Germany	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Hong Kong	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Hungary	Hoffmann-La Roche, Inc.	17 Mar 2021
Multiple sclerosis relapse	Phase 3	Italy	Hoffmann-La Roche, Inc.	17 Mar 2021

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05119569 (FENopta, AAN2025)	Phase 2	Multiple sclerosis relapse	99	Fenebrutinib 200 mg	lvhdnwucuo(izzjnqibtx) = An asymptomatic alanine transaminase elevation occurred newly in one OLE participant (1%) that resolved pkpwmdnwbb (tcenqupdgm ) View more	Positive	07 Apr 2025
				Placebo
NCT05119569 (FENopta-OLE, GlobeNewswire) Manual	Phase 2	Multiple sclerosis relapse	109	Fenebrutinib	yzikxxvabw(hjigoheiuc) = bjhwredrib bsdnieqdhf (udumvmwltj ) View more	Positive	04 Sep 2024
AAN2024	Phase 1	-	-	Fenebrutinib 400 mg	twrcxbfmya(yrbvibsocv) = Both doses were well tolerated, and no serious adverse events (AEs), AEs of special interest or Grade ≥2 AEs were reported bkieryiuju (hzjsmpvump )	Positive	09 Apr 2024
				Fenebrutinib 700 mg
NCT04586010 (FENhance, Biospace) Manual	Phase 3	Multiple sclerosis relapse	-	fenebrutinib	socqvrrqal(ydfsmvhgzy) = wbujbkujkk qmuzfdofis (gmzogzrcvr )	Negative	05 Dec 2023
NCT05119569 (FENopta, ECTRIMS2023) Manual	Phase 2	Multiple Sclerosis	106	Fenebrutinib 200 mg	ajfhydrine(ytqpcpbqra) = eawguagpgy hihsfohifr (xvtedccyou ) View more	Positive	17 Oct 2023
				Placebo	ajfhydrine(ytqpcpbqra) = jyycdynawt hihsfohifr (xvtedccyou ) View more
NCT03407482 (CTgov)	Phase 2	Systemic Lupus Erythematosus	160	GDC-0853	mnhaxxnmel = ogvizelurl binqpmtfij (ilmrbvyjyy, mopoagjuyz - jagsyiptmj) View more	-	19 Dec 2020
ECTRIMS2020	Not Applicable	Multiple Sclerosis	-	Fenebrutinib	ydrmfmqoer(nqslxhuwsm) = pdruxqzgck ziypcrhygh (yoiypinpwj ) View more	-	07 Dec 2020
NCT03137069 (CTgov)	Phase 2	Chronic Urticaria	134	Placebo (Cohort 1: Placebo)	sdflirtvfk(jcqjhfcqgo) = pbwjxjxmws tjrmdnuwgx (nepryhzmcn, 13.49) View more	-	29 Sep 2020
				GDC-0853 (Cohort 1: GDC-0853 200mg BID)	sdflirtvfk(jcqjhfcqgo) = lssipvtrce tjrmdnuwgx (nepryhzmcn, 9.74) View more
NCT03693625 (CTgov)	Phase 2	Chronic Urticaria	31	GDC-0853 (Parent Study: GDC-0853)	rxsnqchejv = cwmqqengnk tnhjymtuho (acbibhrtnb, pdmhutklny - ffivhfobno) View more	-	25 Sep 2020
				GDC-0853 (Parent Study: Placebo)	rxsnqchejv = mktinhabhx tnhjymtuho (acbibhrtnb, vslonwobig - cwqsnttwkq) View more
NCT02983227 (CTgov)	Phase 2	Rheumatoid Arthritis	496	GDC-0853 (GDC-0853 (200mg BID) Cohort 1)	utowqlwstr = fuyprochgs hngxatvmvj (zevrhqybnj, zvxvglilme - mxbblipcwg) View more	-	03 Aug 2020
				GDC-0853 (GDC-0853 (200mg BID) Cohort 2)	utowqlwstr = cxnbdsribn hngxatvmvj (zevrhqybnj, dxiajdxbeo - uqpuxzaphq) View more

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