Year: 2022

CAMBRIDGE, Mass. – March 25, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today presented data from the Phase 1b clinical trial of its investigational oral allosteric tyrosine kinase 2 (“TYK2”) inhibitor, NDI-034858, in patients with moderate-to-severe plaque psoriasis at the 2022 American Academy of Dermatology (AAD) Annual Meeting.

The study enrolled 26 patients with moderate-to-severe plaque psoriasis and was completed in April 2021. Patients received once-daily doses of either NDI-034858 (5mg, 10mg, or 30mg) or placebo over 28 days. As a Phase 1 study, the primary objective was evaluation of safety, and NDI-034858 was observed to be generally well tolerated. No serious adverse events were observed and no trends of adverse events were noted with increasing drug exposure. Most treatment-emergent adverse events were mild or moderate in severity.

Nimbus’ data indicate that treatment with NDI-034858 resulted in improvement across multiple measures of disease pathology and normalization of molecular and inflammatory pathways dysregulated in psoriasis. Additionally, NDI-034858 showed a dose-dependent trend in exploratory clinical activity, measured by mean percent decrease in Psoriasis Area and Severity Index score at four weeks.

In patients treated with NDI-034858, investigators observed decreased thickness of lesional skin epidermis and decreased Ki67 expression (a marker of cell proliferation), as well as resolution of elevated keratin-16 expression. mRNA analyses of skin biopsies showed decreased expression of several psoriasis-related genes and up to 50% improvement in the expression of skin transcriptomes previously associated with psoriasis in lesional skin through microarray analysis. The poster, titled “Analysis of histologic, molecular and clinical improvement in moderate-to-severe psoriasis: Results from a Phase 1b trial of the novel allosteric TYK2 inhibitor NDI-034858,” is on display through March 27, 2022.

“TYK2 plays a central role in both innate and adaptive immune responses and we believe is a promising target for treating a wide range of autoimmune and inflammatory diseases,” said Bhaskar Srivastava, M.D., Ph.D., Vice President of Early Clinical Development at Nimbus. “We are pleased to see the advancement of our allosteric TYK2 inhibitor program, which we believe supports our further development of this candidate as a potential oral treatment option for patients with moderate-to-severe plaque psoriasis.” 

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company that designs and develops breakthrough medicines through its powerful and comprehensive computational drug discovery engine. Nimbus’ pipeline is comprised of multiple selective small molecule compounds targeting proteins that are known to be fundamental drivers of pathology in highly prevalent human diseases and have proven difficult for drug makers to tackle. Nimbus is headquartered in Cambridge, MA. To learn more about Nimbus, please visit www.nimbustx.com.

About the Nimbus TYK2 Program

TYK2 is an important signal-transducing kinase that mediates immune signaling and is important in both adaptive and innate immune cells. TYK2 inhibition is a potentially promising treatment approach for a wide range of autoimmune and inflammatory diseases due to the protein’s central role in both the innate and adaptive immune responses.

Nimbus is conducting two clinical studies to evaluate its novel allosteric TYK2 inhibitor, including an ongoing moderate-to-severe plaque psoriasis (NCT04999839) study and the recently initiated active psoriatic arthritis (NCT05153148) study. The psoriatic arthritis Phase 2b trial is a randomized, multicenter, double-blind, placebo-controlled study that will evaluate three dose levels of the investigational therapy taken orally once per day. It is planned to enroll approximately 260 subjects, with a primary endpoint of proportion of subjects achieving at least an American College of Rheumatology 20 response at week 12. Additional trial details can be found by visiting ClinicalTrials.gov.

Media Contacts:

Chris Railey, (617) 834-0936
Ten Bridge Communications
chris@tenbridgecommunications.com 

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CAMBRIDGE, Mass. – February 3, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the successful generation of multiple, high-resolution protein structures of Werner syndrome helicase (WRN). WRN is a helicase required for DNA replication and repair and a validated target for tumors with microsatellite instability (MSI). Nimbus’ proprietary WRN structures reveal protein motion and provide insights into novel mechanisms of inhibition that have yielded confirmed hits progressing to lead-like chemical matter.

“Our progress in discovery efforts against WRN is a prime demonstration of how Nimbus’ structure-guided approach could enable the identification of both active-site and allosteric inhibitors, even against targets that have historically been challenging to drug,” said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. “While precedence for pharmacological helicase inhibition is limited, WRN is amenable to structural biology, which provides a strong opportunity to develop agents to treat this important subset of solid tumors.”

In addition to the progress Nimbus has made against WRN helicase, Nimbus announced the expansion of its leadership team in computational chemistry with the appointment of Daniel Price, Ph.D., to the newly created role of Executive Director, Head of Computational Chemistry. In this role, Dr. Price will direct the strategic implementation and expansion of Nimbus’ computational capabilities as part of its structure-based drug discovery approach.

“Nimbus’ computational drug discovery engine is distinguished by its ability to integrate a broad set of computational technologies with world-class capabilities in molecular sciences, including biophysics, biochemistry and structural biology, and a deep expertise in medicinal chemistry,” said Dr. Tummino. “The addition of Dan to our leadership team will further bolster our integration of the most advanced computational tools available with our broad drug discovery and therapeutic area expertise.”

Prior to joining Nimbus, Dr. Price spent over 15 years at GlaxoSmithKline, most recently as Director, Computational Chemistry. During his tenure at GSK, he contributed to the discovery of four clinical-stage drug candidates in four distinct therapy areas. In addition to his expertise in structure-based drug discovery and ligand-based drug discovery, Dr. Price has specialized experience in kinase targeting, cross-domain informatics, and ADME modeling. He earned his Ph.D. in molecular biophysics and biochemistry from Yale University and his bachelor’s degree in chemical engineering from the University of Colorado, Boulder. He completed his postdoctoral research fellowship at the Scripps Research Institute.

“Nimbus is a recognized leader in the field of drug discovery, and I’m excited to continue expanding the company’s capabilities in combining cutting-edge computational technology with deep molecular sciences expertise,” said Dr. Price. “I look forward to working alongside Nimbus’ talented team in advancing the company’s diverse portfolio of potential breakthrough medicines.”

Media Contacts:

Chris Railey, (617) 834-0936
Ten Bridge Communications
chris@tenbridgecommunications.com 

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company that designs and develops breakthrough medicines through its powerful and comprehensive computational drug discovery engine. Nimbus’ pipeline is comprised of multiple potent and selective small molecule compounds targeting proteins that are known to be fundamental drivers of pathology in highly prevalent human diseases and have proven difficult for drug makers to tackle. Nimbus is headquartered in Cambridge, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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CAMBRIDGE, Mass. – January 6, 2022 – Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through its powerful computational discovery engine, today announced initiation of a Phase 2b study of the company’s investigational oral allosteric TYK2 inhibitor in patients with active psoriatic arthritis. The study represents the second of Nimbus’ planned clinical trials within its TYK2 franchise, alongside a Phase 2b study in moderate-to-severe plaque psoriasis, which initiated dosing in August 2021.

“Nimbus is excited to commence this new TYK2 clinical study as part of our efforts to evaluate patient impact of our oral allosteric TYK2 inhibitor,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “We believe allosteric TYK2 inhibitors offer immense promise as a new class of medicines that are designed to selectively inhibit TYK2 and potentially treat serious autoimmune and inflammatory conditions.”

Nimbus’ allosteric TYK2 inhibitor has demonstrated highly selective inhibition of TYK2 with little evidence of off-target effects in preclinical studies. In Phase 1 studies, Nimbus’ allosteric TYK2 inhibitor has been generally well tolerated and has shown exploratory signals of clinical activity consistent with what is expected of an allosteric TYK2 inhibitor. Nimbus will be presenting data from its Phase 1 studies at the upcoming American Academy of Dermatology annual meeting in March 2022.

“Nimbus is pleased to initiate the second Phase 2b trial with our allosteric TYK2 inhibitor and to further expand our potential impact in addressing serious autoimmune and inflammatory conditions,” said Bhaskar Srivastava, M.D., Ph.D., Vice President of Early Clinical Development at Nimbus. “Many patients with active psoriatic arthritis are not adequately treated, and there is a need for safe and effective oral treatment options.”

Furthermore, Nimbus Therapeutics and Celgene Corporation, a wholly owned subsidiary of Bristol Myers Squibb, reached an agreement resolving all legal claims and business interests between the two companies pertaining to Nimbus’ TYK2 inhibitor. Nimbus retains all rights to its TYK2 inhibitor program and remains solely responsible for continuing progress through clinical development.

Nimbus will present at the virtual 40th Annual J.P. Morgan Healthcare Conference at 9:00 a.m. ET / 6:00 a.m. PT on Monday, January 10, 2022. CEO Jeb Keiper will provide an overview of the company’s progress and anticipated milestones for 2022 and beyond.

Media Contact:

Chris Railey, (617) 834-0936
Ten Bridge Communications
chris@tenbridgecommunications.com 

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company that designs and develops breakthrough medicines through its powerful and comprehensive computational drug discovery engine. Nimbus’ pipeline is comprised of multiple potent and selective small molecule compounds targeting proteins that are known to be fundamental drivers of pathology in highly prevalent human diseases and have proven difficult for drug makers to tackle. Nimbus is headquartered in Cambridge, MA. To learn more about Nimbus, please visit www.nimbustx.com.

About the Nimbus TYK2 Program

TYK2 (tyrosine kinase 2) is an important signal-transducing kinase that mediates immune signaling and is important in both adaptive and innate immune cells. TYK2 inhibition is a potentially promising treatment approach for a wide range of autoimmune and inflammatory diseases due to the protein’s central role in both the innate and adaptive immune responses.

Nimbus presently has two active clinical trials evaluating its novel allosteric TYK2 inhibitor, an ongoing moderate-to-severe plaque psoriasis (NCT04999839) study and the recently initiated active psoriatic arthritis (NCT05153148) study. The psoriatic arthritis Phase 2b trial is a randomized, multicenter, double-blind, placebo-controlled study that will evaluate three dose levels of the investigational therapy taken orally once per day. It is planned to enroll approximately 260 subjects, with a primary endpoint of proportion of subjects achieving at least an American College of Rheumatology (ACR) 20 response at week 12. Additional trial details can be found by visiting ClinicalTrials.gov.

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