Category: Uncategorized

Critical hire at time of major transformation in the company’s evolution

CAMBRIDGE, Mass. – September 30, 2014 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against important, but previously inaccessible drug targets, today announced the appointment of Donald “Don” Nicholson, Ph.D., as Chief Executive Officer. Dr. Nicholson brings more than 25 years of experience as an entrepreneurial scientist and leader with a proven track record of creating and building therapeutic pipeline value.

“Don has deep expertise in the strategic and operational components of complex drug discovery. His keen insight into the scientific and clinical potential of the novel product portfolio at Nimbus will be very advantageous in generating long-term value for the Company,” said Dan Lynch, Executive Chairman of the Nimbus Board of Directors. “We are extremely pleased to leverage Don’s scientific acumen and business vision in his role as CEO.”

To date, Nimbus has built an extensive portfolio of programs in immunology, oncology and metabolic diseases, targeting mechanisms that have been traditionally difficult or intractable. The company is positioned to enter human clinical trials in early 2015 with the first-ever allosteric inhibitor of acetyl-CoA carboxylase (ACC), and will advance other targets and mechanisms aimed at auto-immune disorders and cancer into development. In addition to its core portfolio, Nimbus has secured industry-leading collaborations with such companies as Shire and Monsanto.

“Nimbus has uniquely built an impressive portfolio of novel compounds directed at several of the most important biological targets known to the drug industry. It is thrilling to join the company at such a watershed moment as the lead programs move toward clinical development,” said Dr. Nicholson. “I look forward to working with such a highly respected team of colleagues, Board members and investors to deliver the greatest value of the portfolio to patients.”

Dr. Nicholson joins Nimbus from Merck where he held various strategic, leadership and operational roles in diverse therapeutic areas, including respiratory, inflammation, immunology, bone, endocrine, urology, infectious diseases and neurosciences. He began his career in 1988 at the Merck-Frosst Centre for Therapeutic Research in Montreal and advanced through various positions of increasing responsibility including Vice President & Site Head of the Merck Neurosciences Research site in San Diego, Calif., and most recently as Vice President and Worldwide Discovery Head for the Respiratory & Immunology Franchise, in Kenilworth, N.J. Dr. Nicholson has co-authored more than 150 publications in peer-reviewed scientific and medical journals and is internationally-recognized for his contributions to the field of apoptotic cell death. He received his Ph.D. and an Honors Bachelor of Science degree in biochemistry from the University of Western Ontario, and trained as a Medical Research Council post-doctoral fellow at the University of Munich in Germany. He is the recipient of multiple academic and professional honors.

About Nimbus

Nimbus Discovery Inc., 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 and its robust pre-clinical pipeline currently 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.

DOWNLOAD PRESS RELEASE

First-time data are being presented showing application of selective ACC inhibitors in pre-clinical models of small cell lung cancer and liver cancer

Company successfully leverages cancer metabolism strategy to achieve potent anti-tumor effects in difficult-to-treat cancers; potential for whole new treatment approach

CAMBRIDGE, Mass. – April 1, 2014 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against exciting but previously inaccessible drug targets, today announced that data on its Acetyl CoA Carboxylase (ACC) program will be presented at the 105th Annual Meeting of the American Association for Cancer Research. Nimbus will present data in two abstracts showing activity with ND-646 and ND-654 in non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) respectively. The conference will take place on April 5–9that the San Diego Convention Center, San Diego, California.

Continuous formation of fat as a source of energy is a common feature of tumor cells and is required to meet the demands of a growing tumor. ACC is the rate-limiting enzyme in the synthesis of new fat, and is up-regulated in many types of cancer, making ACC an attractive target for the prevention of tumor growth. Nimbus is the first company that has successfully designed allosteric inhibitors targeting ACC. The Nimbus small molecules have excellent drug-like properties, high potency, and are tissue- targeted, leading to outstanding pharmacology in preclinical models of disease. These preclinical anti-tumor data are especially encouraging given the lack of treatment options available to combat NSCLC and HCC. In particular, a highly potent and targeted treatment for HCC would be a welcome alternative to currently available drugs that have significant side effects and modest efficacy.

Abstract #1427

Title: Liver Selective Acetyl-CoA carboxylase inhibition by ND-654 Decreases

Hepatocellular Carcinoma Development in Cirrhotic Rats

Authors: Danielle K. DePeralta1, Lan Wei1, Geraldine Harriman2, Jeremy Greenwood3, Sathesh Bhat3, William Westlin2, H. James Harwood, Jr.2, Rosana Kapeller2, Kenneth

1. Tanabe1, Bryan C. Fuchs1.

1Massachusetts General Hospital, Boston, MA; 2Nimbus Discovery, Cambridge, MA; 3Schrödinger, New York, NY

Date: Monday, April 7, 2014

Presentation Time: 8:00 AM – 12:00 PM (PT) Location: Hall A-E, Poster Section 18

Summary

• ND-654, an allosteric inhibitor, inhibited the enzymatic activity of both ACC1 (IC50 = 3 nM) and ACC2 (IC50 = 8 nM), and inhibited fatty acid synthesis in HepG2 cells (IC50 = 14 nM) and in rats (ED50 = 0.3 mg/kg)
• This hepatoselective inhibitor reduced tumor burden in hepatocellular carcinoma model by 65%, when rats were treated with 10 mg/kg PO daily for 5 weeks; similar exposures in cirrhotic and tumor tissue were achieved at steady state
• ND-654 significantly improved survival rate of DEN-treated rats with hepatocellular carcinoma
• In conclusion, these results provide further evidence that de novo lipogenesis is an important mediator of hepatic carcinogenesis and that selective inhibition of hepatic ACC is a potential therapeutic strategy for HCC

Abstract #2679

Title: Acetyl-CoA Carboxylase Inhibition by ND-646 Reduces Fatty Acid Synthesis and Inhibits Cell Proliferation in Human Non-Small Cell Lung Cancer Cells

Authors: Robert Svensson1, Geraldine Harriman2, Jeremy Greenwood3, Sathesh Bhat3,

1. James Harwood2, Rosana Kapeller2, Reuben Shaw1.

1Salk Institute for Biological Studies, San Diego, CA; 2Nimbus Discovery, Cambridge, MA; 3Schrödinger, New York, NY

Date: Monday, April 7, 2014

Presentation Time: 1:00 PM – 5:00 PM (PT) Location: Hall A-E, Poster Section 32

Summary

• ND-646, a potent and selective allosteric ACC inhibitor, demonstrated significant anti-proliferative effects in several NSCLC cell types

• This effect was enhanced in de-lipidated media and attenuated when media was supplemented with palmitate, suggesting that the anti-proliferative effects ND- 646 is induced by depletion of cellular fatty acids
• A novel PD biomarker has been identified that can be used to determine target engagement in NSCLC and other tissues in vivo and in vitro
• ND-646 is currently being tested in NSCLC pre-clinical models

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.

DOWNLOAD PRESS RELEASE

Combination approach evaluated with inhibitors of Btk (ibrutinib), PI3Kdelta (GS-1101), and Syk (P505-15)

Data presented at the 55th American Society of Hematology Annual Meeting

CAMBRIDGE, Mass. – December 9, 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 novel Nimbus IRAK4 inhibitor, ND-2158, when combined with the Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, the PI3Kdelta inhibitor GS-1101 or the Syk inhibitor P505-15, works synergistically to induce selective cell death in hematological tumors with L265P activating MyD88 mutation. This genetically-defined patient population can be identified in the clinic prior to treatment, increasing the potential for a positive response.

The synergism of ND-2158 with these three immunokinase inhibitors was presented in ABC-DLBCL tumor cells at the 55th American Society of Hematology Annual Meeting being held at the Ernest N. Morial Convention Center, New Orleans, La. Nimbus previously demonstrated this synergistic benefit with ibrutinib. This current study extends the potential drug combinations in Nimbus’ ongoing pursuit of more efficacious, less toxic, treatments for lymphoid malignancies that broaden the magnitude and durability of response.

Abstract #3833
Title: Synergistic Blockade of Activated B Cell-Like DLBCL Proliferation with a Selective Inhibitor of IRAK4 in Combination with Inhibition of the B-Cell Receptor Signaling Network
Date: Monday, December 9, 2013
Presentation Time: 6:00 PM – 8:00 PM
Location: Ernest N. Morial Convention Center, Hall E

“Nimbus is working in one of the most exciting areas of oncology drug development. There is significant potential for drugs that are targeted at specific cancer-causing mutations and can be used in synergistic combinations.” said Rosana Kapeller, M.D., Ph.D., Chief Scientific Officer of Nimbus. “We are the first drug developer to identify and optimize highly selective IRAK4 inhibitors with robust potency, and we now have encouraging synergistic data that shows the opportunity for combination with other emerging targeted therapeutics. We currently have multiple, novel IRAK4 inhibitors under evaluation and look forward to moving one of the candidates into the first phase of clinical trials 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. The company has been named by FierceBiotech as one of 2013&tsquo;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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE

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.

DOWNLOAD PRESS RELEASE