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BOSTON, Mass. – March 20, 2023 – Results from the Phase 2b clinical trial of TAK-279 (formerly NDI-034858), a novel allosteric TYK2 inhibitor developed by Nimbus Therapeutics and owned by Takeda (TSE:4502/NYSE:TAK), in patients with moderate-to-severe plaque psoriasis were presented on Saturday, March 18, 2023 at the 2023 American Academy of Dermatology (AAD) Annual Meeting in New Orleans.

The results were presented as part of the Late-Breaking Research session by April Armstrong, M.D., MPH, clinical investigator in the Phase 2b study and Associate Dean and Professor of Dermatology at the University of Southern California.

From Takeda’s press release dated March 18th:

In the Phase 2b study, 259 patients were randomized (1:1:1:1:1 ratio) to receive one of four doses of TAK-279 once-daily, or placebo for 12 weeks. Results showed:

• A significantly greater proportion of TAK-279 patients achieved PASI 75 (44%, 68%, 67%; 5mg, 15mg, 30mg, respectively) versus placebo (6%; p<0.001), meeting the study’s primary endpoint.
• A significantly greater proportion of TAK-279 patients achieved PASI 90 (21%, 45%, 46%; 5mg, 15mg, 30mg, respectively) versus placebo (0%; p<0.001), and PASI 100 (10%, 15%, 33%; 5mg, 15mg, 30mg, respectively) versus placebo (0%; p<0.001 at 30mg).
• A significantly greater proportion of TAK-279 patients achieved Physician Global Assessment (PGA) scores of 0/1 (27%, 49%, 52%; 5mg, 15mg, 30mg, respectively) or 0 (10%, 15%, 33%; 5mg, 15mg, 30mg, respectively) versus placebo (4% [p≤0.001] and 0% [p<0.001 at 30mg], respectively) at 12 weeks. A PGA score of 1 indicates almost clear skin and 0 indicates totally clear skin.
• There were no statistically significant differences in PASI or PGA response rates seen in the TAK-279 2mg arm (18%, 2%, 10%, 2%; PASI 75, PASI 100, PGA 0/1, PGA 0, respectively) compared to placebo.

“We are thrilled to see this data shared with the scientific community, underscoring this medicine’s potential to address the high unmet need among patients with psoriasis and other immune-mediated diseases,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “This marks a turning point to the next ‘chapter’ of Nimbus. We have advanced our leading-edge technologies and grown our expertise in small molecule drug development to deliver breakthrough medicines, by design, for the benefit of patients.”

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, inflammatory and autoimmune conditions and metabolic diseases. Nimbus is headquartered in Boston, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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BOSTON, Mass. – February 8, 2023 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the closing of Takeda’s (TSE:4502/NYSE:TAK) acquisition of Nimbus Lakshmi, Inc., a wholly-owned subsidiary of Nimbus, and its tyrosine kinase 2 (TYK2) inhibitor program, which includes the oral, selective allosteric TYK2 inhibitor NDI-034858, now known as TAK-279. The completion of this acquisition triggered a $4 billion upfront payment from Takeda to Nimbus, which is also eligible to receive up to $2 billion total in sales-based milestone payments.

“We are thrilled to reach this important milestone for what we believe is a best-in-class molecule in the new therapeutic class of oral, selective allosteric TYK2 inhibitors, which has the potential to address high unmet need for patients across a broad range of immune-mediated diseases,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “We look forward to continuing to design future breakthrough medicines, leveraging Nimbus’ unique approach at the intersection of computational chemistry and pharmaceutical sciences, and building on our track record of success.”

Nimbus plans to present detailed data from its Phase 2b clinical trial of NDI-034858 in patients with moderate-to-severe plaque psoriasis at an upcoming medical meeting. Nimbus previously announced that NDI-034858 achieved the trial’s primary efficacy endpoint, with a statistically significant greater proportion of patients reaching PASI-75 (a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index) compared to placebo at 12 weeks.

Nimbus retains ownership of and continues to advance a portfolio of potentially transformative therapeutics for cancer, autoimmune diseases and metabolic disorders, including NDI-101150, a selective hematopoietic progenitor kinase 1 (HPK1) inhibitor, currently being evaluated in a Phase 1/2 study in patients with solid tumors.

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage program, HPK1 (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, inflammatory and autoimmune conditions and metabolic diseases. Nimbus is headquartered in Boston, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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Ten Bridge Communications
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– Nimbus to receive $4 billion in upfront cash, and up to $2 billion in commercial milestone payments –

– NDI-034858 has potential best-in-class profile among new therapeutic class of selective allosteric TYK2 inhibitors for immune-mediated diseases –

BOSTON, Mass. – December 13, 2022 – Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced that it has signed a definitive agreement under which Takeda (TSE:4502/NYSE:TAK) will acquire Nimbus Lakshmi, Inc., a wholly-owned subsidiary of Nimbus Therapeutics, and its tyrosine kinase 2 (TYK2) inhibitor NDI-034858. NDI-034858 is an oral, selective allosteric TYK2 inhibitor being evaluated for the treatment of multiple autoimmune diseases following successful recent Phase 2b results in psoriasis.

“Nimbus’ allosteric TYK2 inhibitor has the potential to be a best-in-class medicine in multiple disease areas, and we are confident that Takeda’s commitment and capabilities will enable NDI-034858 to reach its full value to patients,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “The proposed acquisition highlights Nimbus’ ability to discover and develop high-value investigational medicines leveraging our computational structure-based drug design and development engine. We will continue to advance other exciting target programs in our R&D pipeline — including our selective HPK1 inhibitor, currently in a Phase 1/2 study in patients with solid tumors — as we have done since our founding in 2009.”

Under the terms of the agreement, Takeda will pay Nimbus Therapeutics $4 billion upfront, and sales-based milestone payments up to $2 billion. The transaction is expected to be finalized in the first half of 2023. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976. Nimbus Therapeutics will retain ownership of its other research and development subsidiaries. Takeda will be solely responsible for future development and commercialization of NDI-034858 and other TYK2 inhibitors.

J.P. Morgan Securities LLC is acting as exclusive financial advisor to Nimbus Therapeutics and Goodwin Procter LLP is serving as its legal advisor.

About NDI-034858

NDI-034858 is an allosteric TYK2 inhibitor discovered and developed by Nimbus Therapeutics that is being evaluated for the treatment of multiple autoimmune diseases. In preclinical studies, NDI-034858 has demonstrated exceptional functional selectivity and wide therapeutic margins. In Phase 1 studies, NDI-034858 showed a good tolerability profile, a dose-dependent trend in exploratory clinical activity and a pharmacokinetic profile allowing for once-daily solid oral dosing. Results from Nimbus’ Phase 2b clinical trial in patients with moderate-to-severe plaque psoriasis demonstrated a significantly greater proportion of patients in the study achieving the primary endpoint of PASI-75 (a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index) compared to placebo after twelve weeks of treatment. Data from this trial will be presented at an upcoming medical conference. In addition to psoriasis, NDI-034858 is in an ongoing Phase 2b trial in active psoriatic arthritis (NCT05153148).

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes clinical-stage programs targeting TYK2 and HPK1 (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, inflammatory and autoimmune conditions and metabolic diseases. Nimbus is headquartered in Boston, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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– Once-daily, oral dosing with NDI-034858 achieved statistical significance in the number of moderate-to-severe psoriasis patients achieving PASI-75 compared to placebo –

– Company has readied NDI-034858 for Phase 3 study, planned to begin in 2023 –

 – Results support best-in-class potential of NDI-034858 among allosteric TYK2 inhibitors –

BOSTON, Mass. – November 30, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced positive topline results from a Phase 2b clinical trial evaluating the allosteric TYK2 inhibitor NDI-034858 in patients with moderate-to-severe plaque psoriasis. Data from the 259 patients dosed in the study showed that NDI-034858 achieved the study’s primary efficacy endpoint, with a statistically significant greater proportion of patients reaching PASI-75 (a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index) compared to placebo at 12 weeks. Additional endpoints in the study were successfully achieved and the safety of NDI-034858 was consistent with other leading allosteric TYK2 inhibitors. The company plans to present data from this trial at an upcoming medical conference.

“We are pleased to report success from our Phase 2b psoriasis patient trial that supports NDI-034858’s best-in-class potential among the new class of allosteric TYK2 inhibitors. Additionally the consistent safety profile seen in this study reinforces TYK2 inhibitors as a differentiated non-JAK therapeutic class,” said Bhaskar Srivastava, M.D., Ph.D., Nimbus’ Senior Vice President of Clinical Development. “I’d like to thank the patients, our investigators and collaborators who made this study possible.”

In addition to psoriasis, Nimbus is evaluating NDI-034858 in an ongoing Phase 2b trial in active psoriatic arthritis and intends to launch Phase 3 studies in psoriasis, along with future trials in other autoimmune indications including inflammatory bowel disease (IBD) and lupus.

“The promising topline data from Nimbus’ Phase 2b study provide further evidence that the allosteric TYK2 inhibitor class can deliver effective and safe treatments for patients living with psoriasis,” said April Armstrong, M.D., MPH, clinical investigator in the Phase 2b study and Associate Dean and Professor of Dermatology at the University of Southern California. “I look forward to seeing how the exceptional clinical profile of NDI-034858 may continue benefiting psoriasis patients and the broader autoimmune disease community that potentially stand to benefit from such a differentiated therapy.”

“The success of Nimbus’ allosteric TYK2 inhibitor program demonstrates the company’s ability to discover, design and develop medicines through late-stage development. In addition to NDI-034858, we’re excited about the potential for our selective HPK1 inhibitor, currently being studied in a Phase 1/2 study, to provide an additional treatment option for patients with solid tumors,” said Nathalie Franchimont, M.D., Ph.D., Nimbus’ Chief Medical Officer.

Study Design

This Phase 2b trial (NCT04999839) was designed to assess the efficacy, safety and tolerability of NDI-034858 in patients with moderate-to-severe plaque psoriasis. It was a randomized, multicenter, double-blind, placebo-controlled study that evaluated four dosages of NDI-034858 taken orally once per day. Its primary endpoint was the proportion of patients achieving PASI-75, meaning a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index, at 12 weeks.

About NDI-034858

NDI-034858 is an allosteric TYK2 inhibitor developed by Nimbus Therapeutics that is being evaluated for the treatment of multiple autoimmune diseases. In preclinical studies, NDI-034858 has demonstrated exceptional functional selectivity and wide therapeutic margins. In Phase 1 studies, NDI-034858 showed a good tolerability profile, a dose-dependent trend in exploratory clinical activity and a pharmacokinetic profile allowing for once-daily solid oral dosing. In addition to psoriasis, Nimbus is evaluating NDI-034858 in an ongoing Phase 2b trial in active psoriatic arthritis (NCT05153148).

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes clinical-stage programs targeting TYK2 and HPK1 (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, inflammatory and autoimmune disorders and metabolic diseases. Nimbus is headquartered in Boston, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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Ten Bridge Communications
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CAMBRIDGE, Mass. – October 26, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the appointment of Nathalie Franchimont, M.D., Ph.D., as Chief Medical Officer.

“I am delighted to welcome Nathalie to our leadership team as Nimbus advances multiple potential breakthrough candidates into their next phase of development, including our clinical TYK2 and HPK1 inhibitors,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “Nathalie’s strategic leadership and extensive clinical experience will be an asset to our growing clinical development team, and her wide range of experience in the development and commercialization of both small and large molecules in various therapeutic areas is an ideal fit for the breadth of Nimbus’ pipeline.”

Dr. Franchimont joins Nimbus from Biogen, where she served as Senior Vice President, Head of Multiple Sclerosis and Immunology Development Unit. She previously held a variety of other leadership roles at Biogen, including leading the Multiple Sclerosis Research and Early Development Unit, the New Indications Research and Early Development Unit and the Immunology Drug Innovation Unit. Prior to joining Biogen, Dr. Franchimont held Medical Affairs and Clinical Development roles at Amgen. A rheumatologist by background, Dr. Franchimont trained at the University of Liège and has held research fellow and research associate roles at the University of Connecticut School of Medicine, Yale University School of Medicine and University of Liège. Dr. Franchimont has served on the Board of Directors of OMass Therapeutics since 2020.

“I am incredibly pleased to join Nimbus at a very exciting time in the company’s history and work with this accomplished team to bring new treatment possibilities to patients,” said Dr. Franchimont. “Nimbus has advanced compelling medicines targeting TYK2 and HPK1 to the clinic and is developing strategies to address multiple other highly sought-after targets. NDI-034858, in ongoing Phase 2b trials, is a great example of the power of Nimbus’ approach and I believe it has potential to be a differentiated, best-in-class oral allosteric TYK2 inhibitor for the treatment of psoriasis, psoriatic arthritis and other immune-mediated diseases.”

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus has designed, discovered and developed a diverse portfolio of clinical and preclinical programs focused on inflammatory and autoimmune disorders, cancer and metabolic diseases, including three internally discovered compounds that have advanced into clinical trials. Nimbus is headquartered in Cambridge, MA. To learn more about Nimbus, please visit www.nimbustx.com.

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Ten Bridge Communications
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Nimbus eligible to receive up to $496 million, inclusive of research funding and potential milestone payments, in addition to royalties on net sales

AMPK activation is a promising strategy to treat disorders of dysregulated metabolism

CAMBRIDGE, Mass. – October 11, 2022 – Nimbus Therapeutics, a clinical-stage company that is working to design and develop breakthrough medicines through its powerful computational drug discovery engine, today announced it has entered into a research collaboration and exclusive, worldwide license agreement with Eli Lilly and Company (Lilly) for the development and commercialization of novel targeted therapies that activate a specific isoform of AMPK for the treatment of metabolic diseases.

Leveraging Nimbus’s computational drug discovery engine and expertise in structure-based drug design, Nimbus is uniquely positioned to develop isoform-selective small molecule activators of AMPK with potential therapeutic application to a broad range of metabolic disorders.

“AMPK is a high-value target for the treatment of metabolic diseases, and drug developers have faced challenges for many years in identifying isoform-selective AMPK activators for tissue-specific therapeutic interventions. Nimbus has established a successful track record in developing and progressing highly-selective small molecules to the clinic against hard-to-interrogate targets, which is a demonstration of the power of our computational and structural approach to drug discovery,” said Peter Tummino, Ph.D., Chief Scientific Officer at Nimbus. “We are excited to partner with Lilly and benefit from their deep expertise in metabolic diseases, including diabetes, obesity and related disorders.”

“We look forward to collaborating with this innovative team at Nimbus, which has an established record of developing highly-specific small molecule modulators against important therapeutic targets,” said Ruth Gimeno, Ph.D., Lilly’s Senior Vice President, Diabetes Research and Clinical Investigation. “Developing therapies together that target AMPK helps address a critical need and is part of Lilly’s ongoing efforts to expand treatment options available to patients with metabolic disorders.”

Under the collaboration, Nimbus will be responsible for research activities, and Lilly will be responsible for development and commercialization activities worldwide. Financial consideration for Nimbus includes a series of payments, funding and milestones spread through research, development and commercialization, potentially reaching up to $496 million in total. Nimbus is eligible to receive tiered royalties on global net sales ranging from mid single- to low double-digits.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company working to design and develop 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.

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 – Financing supports ongoing Phase 2b clinical trials of NDI-034858 (allosteric TYK2 inhibitor) and initiation of Phase 3; ongoing Phase 1/2 clinical trials of NDI-101150 (HPK1 inhibitor); and advancement of multiple preclinical programs –

 – Bain Capital Life Sciences and SV Health Investors participating as new investors –

CAMBRIDGE, Mass. – September 12, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the closing of a $125 million private financing. The round involves participation from new investors Bain Capital Life Sciences and SV Health Investors, along with existing investors including Access Biotechnology, Atlas Venture, BVF Partners L.P., Bill Gates, Lightstone Ventures, Pfizer Ventures, RA Capital Management and SR One.

“The strong support from investors in this financing validates the promise and differentiation of Nimbus’ current portfolio of clinical and preclinical programs, and the success of our productive drug discovery engine,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “I’m pleased to welcome SV Health Investors and Bain Capital Life Sciences to Nimbus’ investor syndicate at this very exciting time in our history, and look forward to generating and sharing critical data for our medicines in development in the near term.”

The financing will support the completion of the ongoing Phase 2b clinical trials of NDI-034858, Nimbus’ oral allosteric tyrosine kinase 2 (TYK2) inhibitor, in moderate-to-severe plaque psoriasis and active psoriatic arthritis, the initiation of psoriasis Phase 3 trials, as well as the initiation of additional Phase 2b clinical trials of NDI-034858 in other autoimmune indications, including inflammatory bowel disease (IBD) and lupus.

The financing also will support the ongoing Phase 1/2 clinical trials of NDI-101150, Nimbus’ hematopoietic progenitor kinase 1 (HPK1) inhibitor, in patients with solid tumors, as well as preclinical development of programs targeting Casitas B-lineage lymphoma b (Cbl-b) and Werner syndrome helicase (WRN), along with ongoing discovery efforts across a range of targets.

“We’re proud to lead this financing round to advance Nimbus’ exciting pipeline of clinical and preclinical candidates,” said Nikola Trbovic, Ph.D., Partner at SV Health Investors. “Nimbus has a remarkable track record of success in discovering and developing differentiated small molecule therapies to address substantial unmet medical needs, and we’re excited to support their current portfolio of programs.”

In addition to this financing, Nimbus has recently appointed Gorjan Hrustanovic, Ph.D., Managing Director of BVF Partners, L.P., to its Board of Directors. Dr. Hrustanovic serves on a number of other public and private biotech boards, and trained in cancer biology and translational medicine at the University of California, San Francisco.

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. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus has designed, discovered and developed a diverse portfolio of clinical and preclinical programs focused on inflammatory and autoimmune disorders, cancer and metabolic diseases, including three internally discovered compounds that have advanced into clinical trials. Nimbus is headquartered in Cambridge, MA. To learn more about Nimbus, please visit www.nimbustx.com.

About SV Health Investors

SV Health Investors is a leading healthcare fund manager committed to investing in tomorrow’s healthcare breakthroughs. The SV family of funds invests across stages, geographic regions, and sectors, with expertise spanning biotechnology, dementia, healthcare growth, healthcare technology and public equities. With over $2.5 billion in assets under management and a transatlantic presence with offices in Boston and London, SV has built an extensive network of talented investment professionals and experienced industry veterans. Since its founding in 1993, SV has invested in more than 200 companies with more than 90 of these having achieved successful acquisitions or IPOs. For learn more about SV Health Investors, please visit www.svhealthinvestors.com.

About Bain Capital Life Sciences

Bain Capital Life Sciences (www.baincapitallifesciences.com) invests in pharmaceutical, biotechnology, medical device, diagnostic, and life science tool companies across the globe, with a focus on companies that both drive medical innovation across the value chain and enable that innovation to improve the lives of patients with unmet medical needs. The differentiated skillset of Bain Capital Life Sciences team enables it to deliver targeted capital land value-added strategic support to companies around critical phases of growth and inflections in value. Since 1984, Bain Capital has employed a strategic and analytical approach to identify attractive investment opportunities and partner with management teams to transform and improve their businesses. During this time, Bain Capital has developed global reach, deep expertise, and a proven track record in the life sciences industries across private equity, public equity, credit, venture capital, and real estate.

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Ten Bridge Communications
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CAMBRIDGE, Mass. – August 24, 2022 – Nimbus Therapeutics, a clinical-stage company that is working to design and develop breakthrough medicines through its powerful computational drug discovery engine, today presented research describing the chemical structure of NDI-034858, the company’s investigational oral allosteric TYK2 (tyrosine kinase 2) inhibitor now in two Phase 2b clinical studies for moderate-to-severe plaque psoriasis and active psoriatic arthritis.

The data, presented in an oral session at the American Chemical Society Fall 2022 meeting, describe how Nimbus leveraged structural biology and computational chemistry insights to produce a novel TYK2 inhibitor with a potential best-in-class profile with respect to potency, selectivity and optimized pharmacokinetics/pharmacodynamics properties.

“Challenges in selectivity often arise when the easily druggable target sites are structurally similar to those of other proteins, as is the case with the TYK2 catalytic site. For this reason, we intentionally designed NDI-034858 to target the allosteric JH2 binding site, where key amino acid differences between TYK2 and JAKs 1, 2, and 3 can be exploited to dramatically favor binding to TYK2 over those other closely related kinases,” said Scott Edmondson, Ph.D., Senior Vice President and Head of Chemistry at Nimbus. “Preclinical and clinical data to date support this approach, showing that NDI-034858 can achieve high target inhibition at low clinical doses without evidence of the adverse safety effects observed with JAK inhibition.”

NDI-034858 was developed using structure-based drug design, an approach that applies computational chemistry and other analytical technologies to high-resolution protein-ligand co-crystal structures. Development focused on maximizing the small molecule’s therapeutic benefit by achieving highly selective inhibition of the pseudokinase JH2 domain of TYK2. This allosteric interaction results in very high selectivity compared to the other homologous proteins in the Janus Kinase (JAK) family of non-receptor tyrosine kinases.

“Nimbus’ TYK2 program is an excellent example of our leadership in structure-based drug design. By combining advanced computational methods together with our structural biology and medicinal chemistry expertise, we are able to identify and exploit unique binding pockets on our target proteins to achieve exquisite selectivity,” said Peter Tummino, Ph.D., Chief Scientific Officer at Nimbus. “This approach forms the basis of Nimbus’ diversified portfolio of differentiated candidates in oncology, autoimmune diseases, and metabolic disorders, including our clinical-stage HPK1 program in immuno-oncology and promising preclinical work across numerous targets.”

In a Phase 1 clinical study, NDI-034858 demonstrated a good tolerability profile and evidence of clinical and pharmacodynamic activity across multiple measures of disease pathology in psoriasis. Notably, it has been shown in cellular assays to be significantly more selective than Bristol Myers Squibb’s TYK2 inhibitor deucravacitinib.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company working to design and develop 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 a number of Phase 2 clinical studies to evaluate its novel allosteric TYK2 inhibitor, including an ongoing moderate-to-severe plaque psoriasis (NCT04999839) study and an ongoing psoriatic arthritis (NCT05153148) study. Additional trial details can be found by visiting ClinicalTrials.gov.

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Pharmacokinetic profile supports potential for once-daily dosing in moderate-to-severe psoriasis 

Wide range of doses explore higher ranges of TYK2 inhibition in the clinic than reported by other agents 

CAMBRIDGE, Mass. – May 19, 2022 – Nimbus Therapeutics, a clinical-stage company that is working to design and develop breakthrough medicines through its powerful computational drug discovery engine, today announced the presentation of new data from multiple Phase 1 clinical studies of its investigational oral allosteric tyrosine kinase 2 (TYK2) inhibitor, NDI-034858, in both healthy volunteers and patients with moderate-to-severe psoriasis. The data will be presented in a poster session at the 2022 Society for Investigative Dermatology (SID) Annual Meeting, being held May 18-21, 2022, in Portland, OR.

Data presented at SID reflect analyses of pharmacokinetics, pharmacodynamics, tolerability and clinical activity of NDI-034858. As previously reported, NDI-034858 was observed to be generally well tolerated, and it showed a dose-dependent trend in exploratory clinical activity. The pharmacokinetic profile of NDI-034858 observed in healthy volunteers supports the potential for once-daily dosing, with 50 mg expected to cover IC90 for 24 hours. Additionally, an analysis of the biochemical selectivity of NDI-034858 using proprietary structure-based computational modeling found that Nimbus’ TYK2 inhibitor was highly selective, with approximately 13,000 times more selectivity than deucravacitinib.

“Nimbus’ oral allosteric TYK2 inhibitor has demonstrated exceptional functional selectivity, and has an encouraging clinical activity profile and a favorable tolerability profile. Notably, there is evidence that a single amino acid difference at the allosteric binding pocket may enable greater TYK2 selectivity of NDI-034858 over deucravacitinib,” said Bhaskar Srivastava, M.D., Ph.D., Senior Vice President, Clinical Development at Nimbus. “These results support continued development of this investigational drug candidate as a potential oral treatment option for patients with autoimmune diseases.”

The poster, titled “Characterization of pharmacokinetics, pharmacodynamics, tolerability and clinical activity in Phase 1 studies of the novel allosteric tyrosine kinase 2 (TYK2) inhibitor NDI-034858,” will be presented on Thursday, May 19, from 4:30-6:30 p.m. PT.

Phase 2b clinical studies to evaluate NDI-034858 in moderate-to-severe plaque psoriasis (NCT04999839) and active psoriatic arthritis (NCT05153148) are ongoing.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage company working to design and develop 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 a number of Phase 2 clinical studies to evaluate its novel allosteric TYK2 inhibitor, including an ongoing moderate-to-severe plaque psoriasis (NCT04999839) study and an ongoing psoriatic arthritis (NCT05153148) study. Additional trial details can be found by visiting ClinicalTrials.gov.

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

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CAMBRIDGE, Mass. – April 13, 2022 – Nimbus Therapeutics, a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the expansion of its leadership team with the appointments of Zak Huang as Vice President, Regulatory Affairs, and Gabrielle Poirier as Vice President, Clinical Operations. Nimbus also announced that Bhaskar Srivastava, M.D., Ph.D. has been promoted to Senior Vice President, Clinical Development.

“We’re pleased to welcome Zak and Gabby to Nimbus at such an exciting phase of our company’s growth, and to continue to augment our in-house clinical development expertise. Their breadth of experience in clinical and regulatory leadership will be an asset to our team as we continue to progress three active clinical trials for our novel inhibitors of TYK2 and HPK1,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “I also wish to congratulate Bhaskar on his promotion. Since joining Nimbus he has helped to sharpen our clinical development strategy and to position Nimbus to expand our TYK2 franchise into clinical trials on additional autoimmune and inflammatory diseases.”

“Our highly selective, allosteric TYK2 inhibitor, NDI-034858, has demonstrated favorable tolerability and promising exploratory efficacy in our Phase 1 trials. We are grateful to the patients and investigators in our ongoing Phase 2 studies,” commented Dr. Srivastava.

Dr. Srivastava joined Nimbus in 2021 as Vice President, Early Clinical Development. He previously held senior clinical development roles at the Janssen Pharmaceutical Companies of Johnson & Johnson, where he led a group of physician-scientists responsible for the strategy, design and execution of early-phase clinical programs across indications in dermatology and rheumatology. A board-certified dermatologist, Dr. Srivastava spent five years in clinical practice and was Assistant Professor of Dermatology at the Yale School of Medicine. He holds a bachelor’s degree in biochemical sciences from Harvard University and an M.D. and Ph.D. in immunology from the Perelman School of Medicine at the University of Pennsylvania.

Dr. Huang, Nimbus’ Vice President, Regulatory Affairs, joins from CSL Behring, where he served as Head of Global Product Regulatory Strategy and, subsequently, Head of China R&D, successfully building high-performing teams and driving development and regulatory strategies of new products. His prior regulatory leadership experience includes an 11-year tenure with Merck & Co., where he led global regulatory strategies across multiple therapeutic areas. He earned medical degrees from Nanjing Medical University and practiced medicine as a physician in China.

Ms. Poirier, Nimbus’ Vice President, Clinical Operations, served most recently as Vice President of Clinical Operations for Entasis Therapeutics, where she was responsible for strategic and operational planning of all clinical trials. Her career in biopharma spans more than 20 years, including clinical operations leadership roles with Proteostasis Therapeutics, Alexion Pharmaceuticals, Ironwood Pharmaceuticals and Vertex Pharmaceuticals. Ms. Poirier earned a bachelor’s degree in business administration from Southern New Hampshire University.

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 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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