— First-in-class oral inhibitor designed to selectively target SIK2 to suppress inflammation and promote resolution and tissue repair —

— Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of NDI-225673 in healthy volunteers —

BOSTON, Mass. — November 10, 2026 — Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a computational drug discovery company developing breakthrough small molecule medicines through advanced structure-based design and AI-enabled chemistry, today announced that the first subjects have been dosed in its Phase 1 clinical trial of NDI-225673, an investigational, oral, highly selective inhibitor of salt-inducible kinase 2 (SIK2) for the potential treatment of immune-mediated inflammatory diseases. The Phase 1 trial is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of NDI-225673 in healthy volunteers.

Salt-inducible kinases (SIKs) comprise three closely related isoforms (SIK1, SIK2, and SIK3). SIK2 regulates transcriptional programs involved in inflammatory responses and their resolution, particularly in myeloid cells such as macrophages. In preclinical studies, selective SIK2 inhibition suppressed a broad set of key inflammatory drivers, including TNFα, IL-6, IL-23, and IL-1β, many of which are validated targets of approved biologics for inflammatory diseases. Additionally, selective SIK2 inhibition increased IL-10 and tissue-repair mediators, including amphiregulin (AREG) and thrombospondin-1 (THBS1), supporting its potential to combine broad anti-inflammatory activity with resolution and tissue repair.

In preclinical studies, NDI-225673 demonstrated potent nanomolar cellular activity and high selectivity for SIK2, supporting its potential to minimize potential liabilities associated with inhibition of other SIK isoforms.

“Many patients with immune-mediated inflammatory diseases, such as ulcerative colitis and rheumatoid arthritis, do not reach durable remission on current therapies,” said Peter Tummino, Ph.D., President of Research and Development at Nimbus. “Our goal with selective SIK2 inhibition is to go beyond suppressing individual inflammatory cytokines by engaging biological pathways that regulate inflammation and tissue repair. NDI-225673 represents years of research to achieve a high degree of SIK isoform selectivity, and this Phase 1 study gives us the opportunity to begin testing the SIK2 hypothesis directly in humans.”

 

About NDI-225673

NDI-225673 is an investigational, oral, highly selective small molecule inhibitor of SIK2, designed using Nimbus’ proprietary high-resolution crystal structures to target SIK2 while sparing SIK1 and SIK3. SIK1 inhibition has been associated with cardiovascular risk, and SIK3 loss of function with skeletal and fertility-related defects. These findings suggest that selectively targeting SIK2 may offer a more favorable therapeutic profile in inflammatory disease.

In preclinical studies, selective SIK2 inhibition with NDI-225673 broadly suppressed multiple pro-inflammatory cytokines while inducing the anti-inflammatory cytokine IL-10 and tissue-repair mediators in human macrophages. In mouse models of colitis, SIK2 inhibition reduced disease activity and improved markers of gut barrier integrity, including mucin and occludin, and in a mouse arthritis model SIK2 inhibition reduced joint inflammation. By combining anti-inflammatory activity with resolution and tissue repair, NDI-225673 has the potential to address immune-mediated inflammatory diseases in gastroenterology, rheumatology, and dermatology.

 

About Nimbus Therapeutics

Nimbus Therapeutics is a leader in computational drug discovery, developing breakthrough small molecule medicines against well-validated, difficult-to-drug targets. Nimbus brings together deep expertise in structure-based drug discovery and advanced computational chemistry with AI- and machine learning-enabled predictive modeling in a proven drug discovery engine designed to create differentiated medicines across multiple therapeutic areas.

Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 clinical development for microsatellite instability-high (MSI-H) solid tumors; NDI-225673, a salt-inducible kinase 2 (SIK2) inhibitor in Phase 1 clinical development for inflammatory and autoimmune diseases; and multiple preclinical programs across oncology, immunology, and metabolic diseases. Nimbus is headquartered in Boston, Massachusetts. To learn more, visit www.nimbustx.com.

Media Contact

Cindy Fung, Ph.D.

Nimbus Therapeutics

cindy.fung@nimbustx.com

— Selective SIK2 inhibitors reduced disease activity in a mouse model of rheumatoid arthritis to levels comparable to approved therapies etanercept and upadacitinib —

BOSTON, Mass. — November 5, 2026 — Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a computational drug discovery company developing breakthrough small molecule medicines through advanced structure-based design and AI-enabled chemistry, today announced that it will present new preclinical data from its highly selective salt-inducible kinase 2 (SIK2) inhibitor program in rheumatoid arthritis (RA) at ACR Convergence 2026, the annual meeting of the American College of Rheumatology, taking place November 6–11, 2026, in Orlando, Florida.

SIK2 regulates transcriptional programs involved in inflammatory responses and resolution, particularly in myeloid cells such as macrophages, which contribute to joint inflammation in RA. The preclinical data show that Nimbus’ highly selective SIK2 inhibitors act on two mechanisms relevant to RA: inflammatory responses in human immune cells and the differentiation of osteoclasts, the cells responsible for bone erosion. In a mouse collagen-induced arthritis model, selective SIK2 inhibitors dosed after disease onset reduced paw swelling, joint inflammation, and synovial hyperplasia to levels comparable to the TNFα inhibitor etanercept and the JAK1 inhibitor upadacitinib, both approved treatments for RA.

“These data show that the activity of selective SIK2 inhibition may translate to differentiated efficacy in rheumatoid arthritis, addressing two distinct mechanisms of the disease: inflammation driven by myeloid cells and bone loss driven by osteoclasts,” said Peter Tummino, Ph.D., President of Research and Development at Nimbus. “Together with our earlier preclinical findings in inflammatory bowel disease, these latest results support selective SIK2 inhibition as a novel oral therapeutic approach across immune-mediated inflammatory diseases. We look forward to sharing these results with the rheumatology community at ACR Convergence.”

Poster Presentation Details:

Abstract Title: Selective SIK2 Inhibition Suppresses Inflammation and Disease in Mouse and Human Models of Rheumatoid Arthritis

Abstract Number: 0088

Session: Rheumatoid Arthritis – Translational Models and Mechanisms, Poster Session A

Date and Time: Sunday, November 8, 2026, 10:30 a.m. – 12:30 p.m. ET

Location: Room WB1&2

Presenter: Leon Collis, Ph.D., Executive Director, Biology

The poster will be available on the Nimbus website here following the presentation.

 

About Nimbus Therapeutics

Nimbus Therapeutics is a leader in computational drug discovery, developing breakthrough small molecule medicines against well-validated, difficult-to-drug targets. Nimbus brings together deep expertise in structure-based drug discovery and advanced computational chemistry with AI- and machine learning-enabled predictive modeling in a proven drug discovery engine designed to create differentiated medicines across multiple therapeutic areas.

Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 clinical development for microsatellite instability-high (MSI-H) solid tumors; a salt-inducible kinase 2 (SIK2) inhibitor program for inflammatory and autoimmune diseases; and multiple preclinical programs across oncology, immunology, and metabolic diseases. Nimbus is headquartered in Boston, Massachusetts. To learn more, visit www.nimbustx.com.

Media Contact

Cindy Fung, Ph.D.

Nimbus Therapeutics

cindy.fung@nimbustx.com

— Lizabeth Leveille, M.S., MBA, appointed Chief Business Officer —

— Fang Wang, Ph.D., named Senior Vice President, Head of Biology —

— Daniel Price, Ph.D., promoted to Senior Vice President, Head of Chemistry —

 

BOSTON, Mass. — October 13, 2026 — Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a computational drug discovery company developing breakthrough small molecule medicines through advanced structure-based design and AI-enabled chemistry, today announced three leadership appointments as the company expands its business development and research capabilities and advances its pipeline of novel small molecules, including its highly selective salt-inducible kinase 2 (SIK2) inhibitor program. Lizabeth Leveille, M.S., MBA, has been appointed Chief Business Officer; Fang Wang, Ph.D., has joined Nimbus as Senior Vice President, Head of Biology; and Daniel Price, Ph.D., has been promoted to Senior Vice President, Head of Chemistry.

“Nimbus is at an exciting and important phase in the evolution of our pipeline across multiple therapeutic areas, with our WRN program showing encouraging depth and durability of response in cancer patients, our SIK2 program approaching first-in-human studies for inflammatory and autoimmune diseases, and several other promising early-stage programs advancing against difficult-to-drug targets,” said Abbas Kazimi, M.S., Chief Executive Officer of Nimbus. “As our pipeline continues to mature, Liz’s strategic leadership and deep business development experience will be invaluable as we pursue opportunities to maximize the potential of our science and create value for Nimbus.”

“Fang has a remarkable track record of leading strong biology teams and advancing programs from discovery into the clinic,” said Peter Tummino, Ph.D., President of Research and Development at Nimbus. “As our Head of Biology, she will play a critical role in identifying and advancing compelling targets, deepening our understanding of disease biology, and translating those insights into the next generation of agents in our pipeline.”

“Dan has had a significant impact on Nimbus since joining the company, bringing deep expertise in computational chemistry and structural biology to programs across our pipeline. Nimbus has built one of the industry’s leading computational chemistry capabilities, integrating structure-based drug discovery with AI, machine learning, and predictive modeling. Dan will play a central role in advancing these capabilities further and applying them across our chemistry organization to accelerate the discovery of differentiated medicines for patients in need,” continued Dr. Tummino.

About Lizabeth Leveille, M.S., MBA, Chief Business Officer

Ms. Leveille brings more than two decades of biopharmaceutical business development experience spanning licensing, collaborations and acquisitions across a broad range of therapeutic areas. She joins Nimbus from Merck Research Laboratories, where she most recently served as Vice President, Head of BD&L Boston Innovation Hub and Discovery Transactions, leading early-stage licensing, collaboration and acquisition efforts across Merck’s therapeutic areas. Previously, she spent nearly a decade at Novartis Institutes for BioMedical Research in strategic alliances and transactions. Ms. Leveille is active in the Massachusetts life sciences community and serves on the boards of MassBio and Massachusetts Biomedical Initiatives. She earned an MBA from Babson College and M.S. and B.S. degrees in biotechnology from Worcester Polytechnic Institute.

About Fang Wang, Ph.D., Senior Vice President, Head of Biology

Dr. Wang brings nearly 20 years of experience in precision oncology, cancer immunology and metabolic disease drug discovery and development, spanning both small molecule and biologics programs. She joins Nimbus from HotSpot Therapeutics, where she served as Senior Vice President of Oncology Discovery and Translational Science and helped build the company’s oncology and immunology pipeline, advancing programs from discovery through clinical development. Previously, she was Vice President of Biology and Translational Science at FogPharma, where she advanced oncology programs from discovery into the clinic. Earlier in her career, Dr. Wang spent nearly a decade at Agios Pharmaceuticals, where she served as biology and pharmacology lead for three first-in-class FDA-approved therapies: Tibsovo®, Idhifa®, and Voranigo®. Her work spanned target validation through translational science. She began her industry career at Aveo Pharmaceuticals and earned her Ph.D. in molecular virology from the Chinese Academy of Sciences, followed by postdoctoral research at Harvard Medical School and the Mayo Clinic.

About Daniel Price, Ph.D., Senior Vice President, Head of Chemistry

Dr. Price has been promoted to Senior Vice President, Head of Chemistry, after serving as Vice President, Computational Chemistry and Structural Biology at Nimbus. Since joining the company in January 2022, he has played a key role in advancing Nimbus’s drug discovery programs and strengthening the integration of computational chemistry, structural biology and medicinal chemistry across the portfolio. Prior to Nimbus, Dr. Price spent 16 years at GSK, where he most recently served as Director, Computational Chemistry and contributed to the discovery of four clinical-stage drug candidates across multiple therapeutic areas. His expertise spans structure- and ligand-based drug discovery, kinase targeting, cross-domain informatics and ADME modeling. Dr. Price 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, and completed a postdoctoral research fellowship at Scripps Research.

 

About Nimbus Therapeutics

Nimbus Therapeutics is a leader in computational drug discovery, developing breakthrough small molecule medicines against well-validated, difficult-to-drug targets. Nimbus brings together deep expertise in structure-based drug discovery and advanced computational chemistry with AI- and machine learning-enabled predictive modeling in a proven drug discovery engine designed to create differentiated medicines across multiple therapeutic areas.

Nimbus has advanced multiple internally discovered programs into the clinic and has a track record of successful transactions and collaborations with leading biopharmaceutical companies, including the acquisition of its ACC subsidiary by Gilead Sciences and its TYK2 subsidiary by Takeda, as well as research and licensing collaborations with Eli Lilly and Company.

Nimbus’s pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 clinical development for microsatellite instability-high (MSI-H) solid tumors; a salt-inducible kinase 2 (SIK2) inhibitor program advancing toward first-in-human studies for inflammatory and autoimmune diseases; and multiple preclinical programs across oncology, immunology and metabolic diseases. Nimbus is headquartered in Boston, Massachusetts. To learn more, visit www.nimbustx.com.

 

Media Contact

Cindy Fung, Ph.D.

Nimbus Therapeutics

cindy.fung@nimbustx.com

— Highly selective SIK2 inhibitors demonstrate dual mechanism of suppressing inflammation while promoting pro-resolution and tissue repair pathways —

BOSTON, Mass. — April 16, 2026 — Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a drug discovery company developing breakthrough medicines through AI-enhanced computational chemistry, today announced that it is presenting new mechanistic data on its novel salt-inducible kinase 2 (SIK2) inhibitor program at IMMUNOLOGY2026™, the 109^th annual meeting of the American Association of Immunologists (AAI), taking place April 15–19, 2026, in Boston, Massachusetts.

 

Salt-inducible kinases (SIKs) comprise three closely related isoforms (SIK1, SIK2, and SIK3) that function as key signaling nodes in myeloid cells, integrating pathogen- and damage-associated cues to drive inflammation. Among these, SIK2 plays a critical role in regulating proinflammatory gene expression. Using structure-based drug design, Nimbus has developed highly selective SIK2 inhibitors with greater than 300-fold selectivity over the SIK1 and SIK3 isoforms. Preclinical data demonstrate that selective inhibition of SIK2 drives a dual pharmacological profile in myeloid cells and mice, suppressing proinflammatory cytokines while simultaneously promoting pro-resolution and tissue repair signals, a mechanistic profile distinct from SIK3 and JAK1 inhibition.

 

Presentation Details:

Abstract Title: Selective SIK2 Inhibitors Suppress Proinflammatory Responses While Upregulating Pro-Resolution Signals in Stimulated Myeloid Cells and Mice

Session: Therapeutics for Autoimmune Diseases I

Date: Thursday, April 16, 2026

Time: 2:30 p.m. – 3:30 p.m. ET

Poster Board Number: 556

Session Location: Exhibit Hall

Presenter: Leon Collis, Ph.D.

 

The poster will be available on the Nimbus website here.

 

These findings build on data presented earlier this year at the 21^st Congress of the European Crohn’s and Colitis Organisation (ECCO), where Nimbus reported robust efficacy and protection of the mucosal barrier in mouse colitis models, and anti-inflammatory and tissue repair activity in human ex vivo systems. The IMMUNOLOGY2026 presentation extends that work with a deeper mechanistic characterization, demonstrating that Nimbus’ highly selective SIK2 inhibitors simultaneously downregulate multiple proinflammatory cytokines, including TNFα, IL-23, and IL-6, while upregulating pro-resolution and tissue repair factors, including IL-10. Importantly, this dual effect was not observed with SIK3 inhibition, which instead elevates IL-23 and IL-12, key drivers of inflammatory disease, further highlighting the critical importance of isoform selectivity.

“These data continue to strengthen our conviction that SIK2-selective inhibition is required for this dual mechanism of dampening inflammation and promoting tissue repair,” said Peter Tummino, Ph.D., President of Research and Development at Nimbus. “This distinct profile supports SIK2 inhibition as a differentiated oral therapeutic approach for inflammatory bowel disease and other chronic inflammatory diseases.”

 

Nimbus’ SIK2 program is advancing through investigational new drug (IND)-enabling studies toward first-in-human evaluation in inflammatory and autoimmune diseases.

 

About Nimbus Therapeutics

Nimbus Therapeutics is a structure-based drug discovery company developing breakthrough small molecule medicines through AI-enhanced computational chemistry. Nimbus pursues well-validated but difficult-to-drug targets with high potential to transform patients’ lives. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches.

Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 clinical development for microsatellite instability high (MSI-H) tumors, a salt-inducible kinase 2 (SIK2) inhibitor program advancing toward first-in-human studies for inflammatory and autoimmune diseases, and multiple preclinical programs across oncology, immunology, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

 

Media Contact

Cindy Fung, Ph.D.

Nimbus Therapeutics

cindy.fung@nimbustx.com

— New collaboration follows previous Lilly and Nimbus AMPK research collaboration in cardiometabolic disease —

BOSTON, Mass. – January 6, 2026 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a drug discovery company developing breakthrough medicines through its AI-enhanced computational drug discovery engine, today announced it has entered into a multi-year research collaboration and exclusive, worldwide license agreement with Eli Lilly and Company (“Lilly”) to develop a novel oral treatment for obesity and other metabolic diseases.

This new collaboration follows the previous collaboration between Nimbus and Lilly targeting AMPK in cardiometabolic diseases. The companies will now apply Nimbus’ computational chemistry and structure-based drug design approach to an early-stage, small molecule discovery program addressing a significant unmet need in obesity.

“We are pleased to deepen our collaboration with Nimbus, a team that has demonstrated exceptional ability to tackle complex drug discovery challenges,” said Ruth Gimeno, Group Vice President, Diabetes and Metabolic Research and Development at Lilly. “Working together to develop this novel obesity therapy represents an important addition to Lilly’s efforts to advance innovative treatment options for patients with metabolic disorders.”

“At Nimbus, computational scientists, medicinal chemists, pharmacologists and translational biologists work together to integrate AI-driven predictive models with structure-based design to develop novel small molecules with best-in-class potential. This integration has enabled us to consistently deliver optimized clinical candidates for difficult-to-drug targets,” said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. “We are excited to collaborate with Lilly on another program, combining our discovery capabilities with their metabolic disease expertise to bring a much-needed new treatment to people with obesity and make a meaningful difference in their lives.”

Under the terms of the collaboration, Nimbus is eligible to receive upfront and near-term milestone payments totaling $55 million, with eligibility to receive up to approximately $1.3 billion in total including development, commercial, and sales milestone payments, as well as tiered royalties on global net sales.

About Nimbus Therapeutics

Nimbus Therapeutics is a structure-based drug discovery company developing breakthrough small molecule medicines through AI-enhanced computational chemistry. Nimbus pursues well-validated but difficult-to-drug targets with high potential to transform patients’ lives. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches.

Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 development for microsatellite instability high (MSI-H) tumors, a salt-inducible kinase 2 (SIK2) inhibitor advancing toward first-in-human studies for inflammatory and autoimmune diseases, and multiple preclinical programs in oncology, immunology, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

 

Media Contact:

Cindy Fung, PhD

Nimbus Therapeutics

cindy.fung@nimbustx.com

 

BOSTON, Mass. – December 19, 2025 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the completion of dose escalation (Part A) in its Phase 1/2 clinical trial of NDI-219216, the company’s investigational non-covalent Werner syndrome helicase (WRN) inhibitor for the treatment of microsatellite instability-high (MSI-H) tumors.

Data thus far from the dose escalation portion of the trial demonstrated that NDI-219216 has a favorable safety profile, with no dose-limiting toxicities or severe treatment-related adverse events observed through the maximum administered dose (MAD). No maximum tolerated dose (MTD) was reached. Pharmacokinetic and pharmacodynamic data indicated that NDI-219216 achieved robust WRN target engagement for more than 24 hours at multiple dose levels. The company completed dose escalation approximately nine months ahead of schedule, with enrollment continuing to accelerate across global clinical sites.

“Completing dose escalation represents an important milestone in the clinical development of NDI-219216,” said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Oncology at Nimbus. “We are encouraged by the favorable safety profile and robust target coverage that is translating into early clinical activity in patients. The accelerated timeline, driven by strong patient recruitment, underscores the significant unmet need in this patient population. These results reinforce our confidence in NDI-219216’s differentiated profile and its potential to address patients with MSI-H tumors who have limited treatment options. We look forward to sharing clinical data at an upcoming scientific conference.”

The Phase 1/2 clinical trial (NCT06898450) is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced solid tumors. The study is being conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion). With Part A now complete, the trial is advancing to Part B, which will determine the recommended dose(s) for further evaluation.

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a WRN inhibitor in Phase 1/2 clinical development (NCT06898450) and a diverse portfolio of preclinical programs across oncology, immunology, and metabolism, including a SIK inhibitor program and other undisclosed metabolic targets. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

 

Media Contact

Cindy Fung, PhD
Nimbus Therapeutics
cindy.fung@nimbustx.com

– First participants dosed in Phase 1/2 clinical trial –

– Preclinical data supporting best-in-class potential of NDI-219216 to be presented at AACR Annual Meeting 2025 –

BOSTON, Mass. – April 25, 2025 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced that its Phase 1/2 clinical trial of NDI-219216, the company’s investigational non-covalent Werner syndrome helicase (WRN) inhibitor, is actively enrolling and dosing patients with advanced solid tumors.

“The initiation of this clinical trial marks an important milestone in advancing our novel WRN inhibitor program,” said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Head, Oncology at Nimbus. “We are excited to be evaluating NDI-219216 in patients with advanced disease, who currently have limited treatment options when they experience disease progression on standard of care therapies. The trial is actively enrolling across multiple clinical sites, and we look forward to generating important additional safety and efficacy data as we advance this promising candidate through clinical development.”

The Phase 1/2 clinical trial (NCT06898450) is an open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced cancer. The study will be conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion).

Nimbus presented promising preclinical data on NDI-219216 (previously NTX-452) at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in October 2024. The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses observed at low doses in MSI-H tumor models refractory to immunotherapy and chemotherapy.

The company will present new findings comparing covalent versus non-covalent WRN inhibition mechanisms and demonstrating NDI-219216’s superior efficacy across multiple preclinical MSI-H tumor models compared with other clinical-stage WRN inhibitors in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting being held April 25-30, 2025 in Chicago. The poster entitled “NDI-219216: a non-covalent, potent, selective and highly efficacious WRN inhibitor with best-in-class potential for the treatment of MSI-H tumors” highlights key preclinical findings related to NDI-219216, including:

• Demonstration of activity against a potential resistance mutation at Cysteine 727 that could significantly reduce the efficacy of covalent WRN inhibitors
• Robust tumor regression across multiple MSI-H tumor models, including those that are refractory to existing standard of care agents
• Superior efficacy at lower doses and in less responsive MSI-H tumor models compared to other clinical-stage WRN inhibitors

“The data we are presenting at AACR 2025 highlight several important features of our non-covalent WRN inhibitor,” said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. “NDI-219216 has the potential for more durable target engagement than covalent inhibitors and maintains potency against potential resistance mutations. Its superior efficacy across multiple MSI-H tumor models, including those less sensitive to other WRN inhibitors and those refractory to current therapies, reinforces our belief that NDI-219216 represents a best-in-class opportunity with broad potential across multiple MSI-H tumor types with significant unmet need.”

Link to poster here.

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a WRN inhibitor in Phase 1/2 clinical development (NCT06898450) and a diverse portfolio of preclinical programs across oncology, immunology, and metabolism, including a SIK inhibitor program and other undisclosed metabolic targets. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

 

Media Contact

Cindy Fung, PhD
Nimbus Therapeutics
cindy.fung@nimbustx.com

 

BOSTON, Mass. – March 7, 2025 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, today announced the appointment of Abbas Kazimi, MS, as Chief Executive Officer and a member of the Board of Directors, effective immediately. He succeeds Jeb Keiper, MS, MBA, who has stepped down from the position as part of a planned transition.

“We are excited to announce the next chapter in leadership at Nimbus. The board is unanimous in its support of Abbas, who has been a critical leader in the last decade of success at Nimbus. With the recent appointment of Peter Tummino, Ph.D., as President of R&D and the strong leadership team in place, we are confident Abbas will continue to deliver on the company’s mission to bring breakthrough medicines to patients,” said Bruce Booth, D. Phil., Nimbus’ Chairman of the Board of Directors and co-founder. “We thank Jeb for his passion and leadership in driving the accomplishments Nimbus has achieved to date and have immense respect for what he has done to build the Nimbus we know today.”

“After spending over a decade at Nimbus, I couldn’t be more proud of the incredible team we’ve built and our evolution into a world-class small molecule discovery and early development powerhouse,” said Mr. Keiper. “In this next phase of growth, I can think of no better leader than Abbas, who has led this team in creating an incredibly valuable biotech company. I look forward to seeing Nimbus continue to advance its promising pipeline under his leadership while I pursue time with my family, biotech boards, and philanthropies that impact our industry.”

Mr. Kazimi joined Nimbus in 2014 and has served as Chief Business Officer since 2020. During his tenure, he has helped drive key transactions resulting in over $7 billion in upfront and milestone capital from pharmaceutical partners, including the TYK2 sale to Takeda in 2022. He also has been responsible for expanding Nimbus’ computational drug discovery engine through technology alliances that complement the company’s deep expertise in structure-based drug discovery and medicinal chemistry.

“I am honored to lead Nimbus at this pivotal time in the company’s evolution,” said Mr. Kazimi. “Our robust pipeline, anchored by promising programs like our WRN and SIK inhibitors, and our ongoing collaboration with Lilly, continues to validate our approach and strengthen our position in the industry. I’m particularly excited about what Nimbus will continue to discover and advance, as we leverage our computational drug discovery engine to bring innovative medicines for patients.”

 

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in development for microsatellite instability high (MSI-H) tumors, as well as a diverse portfolio of preclinical programs focused on cancer, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

 

Media Contact:

Cindy Fung, PhD

Nimbus Therapeutics

cindy.fung@nimbustx.com

 

BOSTON, Mass. – February 25, 2025 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, today announced the achievement of a significant preclinical milestone. This milestone, achieved in collaboration with Eli Lilly and Company (Lilly), targets a specific isoform of AMP-activated protein kinase (AMPK) for the treatment of cardiometabolic diseases.

AMPK, a key regulator of cellular energy metabolism, has long been recognized as a promising therapeutic target. Despite its potential, developing selective activators of specific AMPK isoforms has remained technically challenging, with previous attempts to effectively drug the target proving unsuccessful. Throughout their collaboration, Nimbus has leveraged its computational approaches and structure-based drug design capabilities to help overcome these historical obstacles.

“Our team has solved a decades-old challenge in drug development with the discovery of a highly selective isoform-specific AMPK activator. This success demonstrates the power of Nimbus’ computational approach to drug discovery combined with Lilly’s deep expertise in cardiometabolic disease. I am excited by the potential of this molecule to make a meaningful difference for patients,” said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. “I look forward to continuing to apply Nimbus’ discovery engine to address targets across metabolic, cardiovascular, and obesity-related diseases.”

In October 2022, Nimbus and Lilly entered into a research collaboration and exclusive, worldwide license agreement for the development and commercialization of small molecule activators of AMPK. Under the terms of the agreement, Nimbus is responsible for research activities and Lilly is responsible for development and commercialization efforts worldwide. Nimbus is eligible to receive research, development, and commercial milestone payments up to $496 million, in addition to royalties on global net sales ranging from mid-single- to low double-digits.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in development for microsatellite instability high (MSI-H) tumors, as well as a diverse portfolio of preclinical programs focused on cancer, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

Media Contact:

Cindy Fung, PhD

Nimbus Therapeutics

cindy.fung@nimbustx.com