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Company presents updated data on unique series of liver-selective ACC inhibitors showing acute and chronic preclinical efficacy, at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases

CAMBRIDGE, Mass. – November 4, 2013 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, will present preclinical data at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), that show the company has optimized a unique series of Acetyl Co-A Carboxylase (ACC) allosteric inhibitors that bind to the BC domain of ACC and demonstrate excellent potency, drug- like properties and preclinical efficacy. The novel, internally-developed small molecules, ND-654 and ND-630, demonstrated desirable in vitro and in vivo efficacy in experimental models of metabolic disease, diabetes and hepatic steatosis. In an iterative design fashion over 16 months, the potency of this family of compounds were improved >1000x utilizing the company’s proprietary small molecule computational drug discovery technology, and drug-like properties were optimized to efficiently deliver development candidate quality molecules.

Simultaneous inhibition of both isoforms of ACC decreases fatty acid synthesis and stimulates fatty acid oxidation and has the potential to favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver diseases including non- alcoholic steatohepatitis (NASH). Nimbus’ ACC inhibitors, including ND-654 and ND- 630, are believed to be the first drug-like allosteric inhibitors to bind the biotin carboxylase (BC) domain of ACC with high potency and selectivity.

Key findings of the Nimbus compounds presented at the conference include:

• ND-654
• Liver specific ND-654 has favorable drug-like properties with a 2700:1 liver to muscle exposure
• Proof-of-mechanism: ND-654 acutely inhibits ACC, with virtually no effect on muscle, resulting in focused pharmacological effects on the liver
• Proof-of-concept: ND-654 demonstrated target engagement in the liver and dose dependently decreased fatty acid production in the liver
• ND-630
• Liver selective ND-630 has favorable drug-like properties with a 100:1 liver to muscle exposure
• Proof-of-mechanism: ND-630 acutely inhibits ACC, demonstrating efficacy in both liver and muscle by preventing malonyl Co-A production
• Proof-of-concept: ND-630 demonstrated target engagement in the liver and muscle
• Dosing of ND-630 in high sucrose fed diet-induced obesity (DIO) rats showed improvement in insulin sensitivity, improvement in hepatic cholesterol and normalization of hepatic triglycerides, dose dependent decrease of plasma triglycerides and FFAs, and decrease in plasma cholesterol

“Within 16 months, Nimbus has become the first company to identify and optimize a broad portfolio of liver directed, small molecule inhibitors of ACC – a previously intractable disease target,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “We are now preparing for ND-630 to enter the clinic in 2015 for the treatment of NASH and diabetes, while we continue to progress ND-654 in preclinical models of hepatocellular carcinoma.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class

life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. The company has been named by FierceBiotech as one of 2013’s Fierce 15, designating it as one of the most promising private biotechnology companies in the industry. For more information please visit www.nimbustx.com.

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Companies Will Focus Efforts on Developing Novel Fungicides

CAMBRIDGE, Mass. and ST.LOUIS – June 27, 2013 – Nimbus Discovery, LLC, a biotechnology company discovering novel approaches for previously inaccessible disease targets, and Monsanto Company, today announced a collaboration to develop broad-spectrum fungicides, with new modes of action, that help farmers control diseases and promote overall plant health.

Fungal infections appear as rusts, leaf spots and blights on a range of important food crops and are estimated to result in significant global crop losses each year.

Under the terms of the agreement, a jointly-owned entity will be created that has access to Nimbus’ validated computational platform. Nimbus, with its innovative research tools together with Monsanto’s agricultural testing capabilities will co-develop agricultural fungicides. Monsanto will have access to applications within agriculture and Nimbus will retain rights for all other applications. Financial terms were not disclosed.

“Working with Monsanto gives Nimbus a unique opportunity to showcase its integrated computational chemistry and drug discovery strengths in the global agricultural marketplace,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “This partnership demonstrates the broad applicability of the Nimbus platform and the ability of the Nimbus team to extract the greatest value from our scientific assets.”

Monsanto’s corporate venture group has an on-going strategic alliance with Atlas Venture, founder of Nimbus Discovery, to explore co-investment opportunities in early-stage life sciences technology companies. This announcement is an investment supported by the alliance.

“Part of our commitment to bringing new technologies to agriculture is identifying innovators we can work with to deliver solutions for our farmer customers,” said Steve Padgette, Monsanto R&D investment strategy lead. “Nimbus is breaking new ground with promising and novel work that has strong potential to be applied in agriculture. We look forward to working with them through this new collaboration, which will complement our own research capabilities.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. Nimbus focuses on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Nimbus’ robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. The company is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

About Monsanto Company

Monsanto Company is a leading global provider of technology-based solutions and agricultural products that improve farm productivity and food quality. Monsanto remains focused on enabling both small-holder and large-scale farmers to produce more from their land while conserving more of our world’s natural resources such as water and energy. To learn more about our business and our commitments, please visit: www.monsanto.com. Follow our business on Twitter^® at www.twitter.com/MonsantoCo, on the company blog, Beyond the Rows^® at www.monsantoblog.com, or subscribe to our News Release RSS Feed.

Monsanto Cautionary Statements Regarding Forward-Looking Information

Certain statements contained in this release are “forward-looking statements,” such as statements concerning the company’s anticipated financial results, current and future product performance, regulatory approvals, business and financial plans and other non-historical facts. These statements are based on current expectations and currently available information. However, since these statements are based on factors that involve risks and uncertainties, the company’s actual performance and results may differ materially from those described or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, among others: continued competition in seeds, traits and agricultural chemicals; the company’s exposure to various contingencies, including those related to intellectual property protection, regulatory compliance and the speed with which approvals are received, and public acceptance of biotechnology products; the success of the company’s research and development activities; the outcomes of major lawsuits and the previously-announced SEC investigation; developments related to foreign currencies and economies; successful operation of recent acquisitions; fluctuations in commodity prices; compliance with regulations affecting our manufacturing; the accuracy of the company’s estimates related to distribution inventory levels; the company’s ability to fund its short-term financing needs and to obtain payment for the products that it sells; the effect of weather conditions, natural disasters and accidents on the agriculture business or the company’s facilities; and other risks and factors detailed in the company’s most recent Form 10-K Report to the SEC. Undue reliance should not be placed on these forward-looking statements, which are current only as of the date of this release. The company disclaims any current intention or obligation to update any forward-looking statements or any of the factors that may affect actual results.

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New Data Presented at the American Diabetes Association 73rd Scientific Sessions Shows Promise for Treatment of Diabetes, Metabolic and Fatty Liver Diseases

CAMBRIDGE, Mass. – June 22, 2013 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, presented preclinical data today that show that the company’s Acetyl CoA Carboxylase (ACC) allosteric inhibitor, ND-630, improves insulin sensitivity; produces a dose dependent reduction in whole body fat markers; and decreases triglycerides, fatty acids and cholesterol in diet-induced models of obesity. The data were unveiled at the American Diabetes Association’s 73rd Scientific Sessions in Chicago, Ill., in poster 636-P/0636 entitled, “Acetyl-CoA carboxylase inhibition by ND-630 inhibits fatty acid synthesis, stimulates fatty acid oxidation, reduces body weight, improves insulin sensitivity, and modulates dyslipidemia in rats.”

ND-630 is believed to be the first drug-like allosteric inhibitor to bind the biotin carboxylase (BC) domain of ACC with high potency and selectivity. Moreover, alignment of the compound’s liver-muscle tissue exposure results in outstanding pharmacology in a metabolic disease model setting. Together, these attributes offer the potential for robust efficacy and safety in a clinical setting.

Key findings of the Nimbus compound presented at the conference include:

• A proprietary state-of-the-art structure-based drug design approach identified allosteric inhibitors of ACC that uniquely bind to the BC domain of ACC
• ND-630 demonstrates in vivo proof of concept in pharmacologically relevant models of diet-induced obesity (DIO)
• ND-630 is fully optimized for excellent potency and drug-like properties

“Nimbus has successfully leveraged its cutting-edge computational platform to create a portfolio of highly potent and selective allosteric ACC inhibitors,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “ND-630 has a significant impact on multiple metabolic disease endpoints, giving us the confidence to progress our ACC program rapidly towards clinical development.”

Download the poster presented by Nimbus Discovery at the 2013 ADA Meeting (PDF File)

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

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Companies Enter Agreement to Co-Develop First-in-Class Small Molecule Therapies for Key Lysosomal Storage Disorders

CAMBRIDGE, Mass. – May 8, 2013 – Nimbus Discovery, LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible disease targets, today announced a co-development agreement with Shire plc focused on small molecule treatments for several rare genetic diseases known as lysosomal storage disorders (LSDs). The goal of the collaboration is to utilize the Nimbus breakthrough computational chemistry approach to discover and develop novel, disease-altering therapies. Many LSDs remain untreated because of challenges in creating drugs that can effectively reach the disease site. The significant potential of this partnership is the development of the first small molecule agents designed to penetrate inaccessible tissues while offering the convenience of an orally-administered pill.

The Nimbus Shire collaboration is the result of a joint assessment of a series of important rare disease targets with significant unmet medical need. One target was ultimately chosen to be the research focus. Under the terms of the agreement, Nimbus will use its cutting-edge research and development platform to extensively profile molecules against the agreed upon disease target and will deliver a drug candidate that is ready to enter late preclinical studies. Nimbus will control and conduct all related research up to achievement of drug candidate status at which point Shire will have an exclusive option to acquire the program. Shire will then be responsible for all clinical development and future commercialization activities. Nimbus is eligible to receive preclinical, development and commercial stage milestones commensurate with the innovative nature of the research and significant unmet medical need of the disease indications.

“This collaboration validates our computationally-driven, structure-based drug discovery engine and innovative partnering model,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “Nimbus is thrilled to pursue our first alliance with Shire, a company that shares our passion for uncovering breakthroughs in highly sought-after disease targets that have proven inaccessible to traditional industry approaches.”

“Nimbus is ground-breaking in their approach to drug discovery and, in a short period of time, have already assembled an impressive track record in delivering clinical candidates for challenging disease targets,” said Dr. Philip J. Vickers, Senior Vice President, Research and Development, Shire. “As a leader in rare diseases, this partnership is another way for Shire to ensure that we expand into new disease areas and continue to apply cutting edge technologies in this space. This agreement complements Shire’s long-term commitment to bring innovative therapies to patients with rare diseases worldwide.”

This is the first deal announced through Shire’s strategic alliance with Atlas Venture, which identifies investments for early stage venture creation around rare genetic diseases.

About Lysosomal Storage Disorders

Lysosomal Storage Disorders are a group of approximately 50 rare inherited metabolic disorders that are caused by a lack of enzymes that normally eliminate unwanted substances in human cells. Lysosomes act as the “recycling center” of each cell, breaking down unwanted material into simple products for the cell to use for building new material. The lack or malfunction of certain enzymes causes a buildup of the molecules that the enzyme would normally eliminate, and deposits accumulate in many cells of the body. Abnormal storage impairs cell function and can cause damage to the body’s cells, which can lead to serious health problems. Lysosomal storage diseases predominantly affect children, many of which die within a few months or years of birth if untreated.

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. Nimbus focuses on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Nimbus’ robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. The company is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

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Scientific Leader to Support Nimbus’ IRAK4 and ACC Programs on Path to IND in 2014

CAMBRIDGE, Mass. – February 6, 2013 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, today announced the appointment of William “Wes” F. Westlin, Ph.D., as Head of Preclinical Research & Early Development. Dr. Westlin joins Nimbus from Celgene, where he was Vice President, Preclinical Research, following Celgene’s acquisition of Avila Therapeutics in 2012.

“Wes is an outstanding scientific leader who will help us accelerate our IRAK4 and ACC programs towards early proof of concept in the clinic,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “He brings broad and highly relevant drug development expertise most recently from Avila’s Bruton’s tyrosine kinase (Btk) and EGFR-mutant selective inhibitor (EMSI) programs. We are tremendously excited to welcome him to Nimbus.”

“Nimbus has clearly demonstrated that it can drug the toughest targets in important, validated pathways and I am convinced that their approach will enable the development of novel therapeutics in oncology, immunology and metabolic disease,” said Dr. Westlin. “I am delighted to join such an outstanding group of collaborative scientists.”

Dr. Westlin has more than 20 years of drug discovery and development experience. During his tenure at Avila, and later Celgene, he was responsible for all of the company’s preclinical efforts, including biology research, pharmacology, toxicology, ADME/PK, and clinical strategic planning. He successfully advanced Avila’s Btk program into Phase 1 development for non-Hodgkin’s lymphoma, B cell chronic lymphocytic leukemia, and rheumatoid arthritis. Dr. Westlin joined Avila in 2007 as the company’s third employee and helped build the R&D department to more than 40 employees. Within this five-year period, Dr. Westlin contributed to more than 10 projects from lead optimization to Phase 1 proof-of-concept, and advanced three programs to IND ready stage.

Prior to joining Avila, Dr. Westlin served as the Senior Vice President for Preclinical Research at Praecis Pharmaceuticals, where he was responsible for preclinical activities in oncology, immunoinflammatory diseases, and Alzheimer’s disease programs. Before joining Praecis, Dr. Westlin held scientific positions of increasing responsibility in the immunology, molecular pharmacology, and oncology research units of Monsanto/Searle and subsequently Pharmacia. He has co-authored more than 40 scientific publications in peer-reviewed journals, has been named a co-inventor on multiple patents and has been invited to deliver scientific presentations around the world. Dr. Westlin also currently serves as a Board member for the Inflammation Research Association. He received his Master’s and Ph.D. in Pharmacology from New York Medical College and his B.S. in Biology from the University of Richmond.

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. Nimbus focuses on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Nimbus’ robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. The company is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

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Company successfully discovered and optimized the first small molecule allosteric inhibitors of ACC achieving excellent potency, selectivity and drug-like properties within 12 months

CAMBRIDGE, Mass. – January 28, 2013 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, will present preclinical data today at the Keystone Symposia Conference: Adipose Tissue Biology in Keystone, Colo., that show that the company has identified a series of novel, highly potent, and highly selective Acetyl CoA Carboxylase (ACC)1/2 allosteric inhibitors. Inhibition of ACC reduces fatty acid synthesis and stimulates fatty acid oxidation and has the potential to favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver diseases.

Most efforts to discover ACC inhibitors have focused on interactions within the carboxyltransferase (CT) domain of the enzyme active center resulting in poor drug-like properties and have thus failed to provide benefit to patients. In contrast, Nimbus focused on the biotin carboxylase (BC) domain where the natural product soraphen interacts. Nimbus ACC allosteric inhibitors demonstrate excellent drug-like properties and show liver-muscle exposure that is aligned with driving outstanding pharmacology in preclinical models of disease.

Key findings of the Nimbus compounds presented at the conference include:

• Development of this series of ACC inhibitors has yielded deep structure-activity relationships, sub-nanomolar enzyme inhibition, functional activity in cellular assays and favorable drug-like properties leading to in vivo proof of concept.
• ND-630, the Nimbus lead compound, potently inhibits hepatic fatty acid synthesis (ED₅₀ = 0.14 mg/kg) in a highly dose-dependent manner and stimulates whole body fatty acid oxidation (minimum effective dose 3 mg/kg) in preclinical models of disease.

“Using our state-of-the art structure-based drug design approach, Nimbus was able to identify potent small molecule ACC inhibitors, with excellent pharmaceutical properties, 12 months after hits were generated from an in silico screen. We believe that we are the first company to create drug-like allosteric inhibitors against ACC. The impressive potency and selectivity of our molecules could translate into significant safety and efficacy benefits in the clinic,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “We are now conducting a detailed pharmacological evaluation of this broad portfolio of potent allosteric inhibitors, including ND-630, and will provide an update on these data in metabolic disease, diabetes and cancer tumor metabolism models in the near future.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

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Potential to increase durability and response rates in lymphoid malignancies
Novel genetically targeted therapy for tumors with activating L265P MyD88 mutation
Data presented at the 54th American Society of Hematology Annual Meeting

CAMBRIDGE, Mass. – December 9, 2012 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible disease targets, will present preclinical data today that show that the novel Nimbus IRAK4 inhibitors (ND-2110 and ND-2158) when combined with the Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, work synergistically to induce selective cell death in hematological tumors with the activating MyD88 mutation. This genetically-defined patient population can be identified in the clinic prior to treatment increasing the potential for positive response. These findings were generated in collaboration with Louis M. Staudt, M.D., Ph.D., Head, Molecular Biology of Lymphoid Malignancies Section at the National Cancer Institute.

IRAK4 and BTK are well-known signaling kinases required for tumor cell survival and proliferation. The synergism of IRAK4 and BTK inhibition was demonstrated in both ABC-DLBCL and Waldenström’s macroglobulinemia tumor cells at the 54^th American Society of Hematology Annual Meeting being held at the Georgia World Congress Center in Atlanta, Ga.

“Nimbus is the first drug developer to uncover the underlying drivers of potency and selectivity for IRAK4, enabling us to identify truly selective IRAK4 inhibitors in less than two years since the company was founded,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “These data highlight that our novel compounds have the potential to treat a genetically identified patient population, who lack effective treatment options, with a highly targeted cancer treatment with improved likelihood of clinical success. We expect to initiate clinical studies in patients with hematological tumors in 2014.”

Abstract #62 IRAK4 Kinase As A Novel Therapeutic Target in the ABC Subtype of Diffuse Large B Cell Lymphoma

Kian-Huat Lim, M.D., Ph.D., Medical Oncology Branch, National Cancer Institute/ National Institutes of Health, Bethesda

Sunday, December 9, 2012: 12:15 PM

B401-B402, Level 4, Building B (Georgia World Congress Center)

• The American Cancer Society estimates there will be 79,190 new patients diagnosed with lymphoma in 2012 and approximately 20,130 deaths
• Oncogenic MyD88 mutations are present in 39% of activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL), and many other lymphoid malignancies
• Oncogenic MyD88^L265P constitutively engages IRAK4/IRAK1 kinases to activate the canonical NF-kB pathway and promote lymphoma cell division and survival
• IRAK4 kinase activity is obligatory for MyD88^L265P-driven oncogenic signaling
• IRAK4 inhibitors are universally toxic towards ABC DLBCL tumors containing MyD88^L265 but not cell lines with wild type MyD88 or germinal center B-cell-like (GCB) DLBCL, consistent with the highly specific mechanism of action.
• ND-2158 is well-tolerated in NOD-SCID mice, and shows single agent activity in a DLBCL xenograft (OCI-LY10)
• The compounds demonstrate good pharmacologic drug-like properties and are expected to have a suitable safety profile for clinical evaluation
• Preclinical data strongly support pharmacologic inhibition of IRAK4 kinase activity as a novel and promising therapeutic strategy for treatment of MyD88-mutated DLBCL, and potentially other lymphoid malignancies
• Combined inhibition of BTK and IRAK4 signaling should be explored as a novel therapeutic strategy in ABC DLBCL

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates. For more information please visit www.nimbustx.com.

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Proprietary physics-based drug discovery technology enabled rapid identification of potent and selective drug candidates for previously inaccessible target

CAMBRIDGE, Mass. – November 12, 2012 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible disease targets, will present data today at the American College of Rheumatology (ACR) Annual Scientific Meeting in Washington, D.C., demonstrating robust efficacy and selectivity of their IRAK4-inhibitors in preclinical models of rheumatic and auto-immune diseases. IRAK4, is a kinase protein, well-validated and long sought after as a target for the treatment of such conditions as lupus, rheumatoid arthritis, psoriasis and inflammatory bowel disease. Previous attempts to identify small molecule modulators of IRAK4 have failed, and yet, the Nimbus compounds show good drug-like properties and are candidates for further development with the potential to make a significant positive impact on patients.

More than 100 conditions fall under the category of rheumatic disease and there are approximately 46 million people in the United States living with some form of the disease. Rheumatic diseases affect the joints and bones and cause chronic joint pain, swelling, and stiffness, and some affect other areas of the body, including the heart, kidneys, lungs, and skin. The drugs currently available to treat most of these conditions do not provide a cure but rather limit the symptoms.

Using a physics-based computational approach, Nimbus and their co-founding partner, Schrödinger Inc., uncovered previously unexploited drivers of potency and selectivity. These insights were used to discover, design, synthesize and test the first truly selective small molecule IRAK4 inhibitors. The three Nimbus novel compounds, ND-346, ND-2110 and ND-2158 demonstrated high selectivity against a panel of 334 kinases, and potent in vitro inhibition of cytokine production in cells and whole blood. Moreover, robust in vivo efficacy was achieved in collagen-induced arthritis, psoriasis and mono-sodium urate (MSU) gout mouse models.

“Previous attempts to modulate IRAK4 have resulted in poor selectivity and inadequate drug-like properties,” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “These data validate Nimbus’ computational approach to drug discovery and demonstrate our ability to quickly and efficiently identify high potential drug candidates for a target that has challenged researchers for more than a decade.”

Download the poster presented by Nimbus Discovery at the 2012 American College of Rheumatology (ACR) Annual Scientific Meeting (PDF File)

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Gates Ventures. For more information please visit www.nimbustx.com.

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Expands Breadth of Nimbus Drug Discovery Network

CAMBRIDGE, Mass. – November 8, 2012 – Nimbus Discovery LLC, today announced that it has executed a Privileged Partnership Agreement with Proteros Biostructures GmbH (“Proteros”), Martinsried, Germany. This partnership will accelerate drug discovery efforts against a growing pipeline of medically important targets.

Nimbus joins a select number of prestigious pharmaceutical and biotechnology companies that have entered into Privileged Partnership Agreements with Proteros. Privileged Partners are able to preferentially access Proteros’ new Gallery Structures, technologies and extensive in-house expertise to accelerate structure-based drug discovery efforts.

Jonathan Montagu, Vice President, Business Development and Operations at Nimbus commented, “Our cutting-edge computational platform relies heavily upon high quality x-ray structure data. Hence, our current collaboration with Proteros has been instrumental in our success with previously inaccessible targets. This expanded partnership is a logical progression of how we are integrating leading edge technologies to create a new model for drug discovery.”

Cony D’Cruz, Chief Business Officer and President, Proteros, US Inc. added, “We are excited to expand our collaboration with Nimbus. The relationship has been very productive and we look forward to continuing to support Nimbus’ innovative and proven discovery platform.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors; including Atlas Venture, SR One, Lilly Ventures and Gates Ventures. For more information please visit www.nimbustx.com.

About Proteros biostructures GmbH

Proteros is a privately held company that provides services and proprietary technologies to support integrated drug discovery. Proteros uses its technical expertise, industrial processes and unique technologies for crystallography, kinetic and thermodynamic profiling and fragment-based lead generation incorporating protein structure inspired compound and fragment libraries. The platform enables ‘knowledge driven lead engineering’ to accelerate and improve protein structure analysis and structure-based drug discovery. Proteros complements its clients’ internal capabilities with external expertise and access to flexible resources. Proteros currently provides services to more than 80 pharmaceutical and biotechnology clients in North America, Europe and Asia. Proteros US, Inc. is a wholly owned subsidiary of Proteros established to serve the growing customer base in North America. For more information please visit www.proteros.com.

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CAMBRIDGE, Mass. – November 1, 2012 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible disease targets, today announced that Daniel S. Lynch has been appointed to the company’s Board of Directors as Executive Chairman. Dan will succeed Bruce Booth, D. Phil., Partner at Atlas Venture and Co-Founder of Nimbus, who will remain on the Board.

“One of Dan’s many strengths is his ability to drive young companies to achieve their goals. In particular, his proven track record in creating value through partnerships will be important as we secure a series of program-focused transactions”, said Bruce Booth. “His expertise in strategy and executive management will provide a valuable resource to the Nimbus team and Board,” Booth added.

Previously, Dan was Executive Chairman at Avila (acquired by Celgene in 2012) and Stromedix (acquired by Biogen Idec in 2012). Dan has more than 25 years experience serving in management positions in the biotechnology and pharmaceutical industries. Dan was CEO and CFO at ImClone Systems, which he led through a significant turnaround, helping to restore the company’s reputation and to secure FDA approval of ERBITUX^® (cetuximab), a novel cancer treatment. Earlier, he served in various financial positions at Bristol-Myers Squibb over a 15-year tenure.

“Nimbus Discovery is successfully developing drugs for sought-after targets where traditional chemistry approaches have failed,” said Dan Lynch. “Nimbus has established a radically new approach to drug discovery that has the potential to transform the entire industry pipeline with innovative medicines.”

About Nimbus

Nimbus Discovery, a biotechnology company, harnesses cutting-edge computational technologies to uncover breakthroughs in small molecule pharmacology. We focus on medically important and highly sought-after disease targets that have proven inaccessible to traditional industry approaches. Our robust pre-clinical pipeline includes novel agents for the treatment of cancer, metabolic disease and inflammation. Nimbus is organized as a constellation of small, nimble teams of experienced drug-hunters deployed across program-focused subsidiary companies. Each team is freed from conventional barriers to scientific success, chartered to create solutions, and geared for program asset deals with leading pharmaceutical companies. Founded in 2009, Nimbus partnered with Schrödinger to invent and apply a physics-based approach that establishes a new standard for rational drug design. Nimbus is backed by world-class life science investors, including Atlas Venture, SR One, Lilly Ventures and Gates Ventures. For more information please visit www.nimbustx.com.

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