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Upcoming AACR and EASL poster presentations support Nimbus’ novel, liver-directed approach to allosteric ACC inhibition across liver disease spectrum, including NASH and HCC

CAMBRIDGE, Mass. – April 21, 2015 – Nimbus Therapeutics announced today that it has initiated a Phase I clinical program for NDI-010976, an allosteric Acetyl CoA Carboxylase (ACC) inhibitor, for the treatment of non-alcoholic steatohepatitis (NASH) and related fatty liver disease-spectrum disorders. The single site, open-label Phase I study is being conducted in healthy human volunteers to assess the safety, pharmacokinetic (PK) behavior and maximum tolerated dose of NDI-010976. A subsequent Phase Ib study will enroll obese patients with metabolic syndrome in order to measure key pharmacodynamic (PD) markers that are relevant to the NASH patient population. Nimbus expects all Phase I studies will be completed this year and Phase II studies will begin early next year.

“We believe that ACC inhibition offers a potentially novel and important approach to the treatment of NASH and related disorders since it precisely targets a key enzyme which is required for the formation of lipids that accumulate in the liver during NASH that drive pathogenesis of the disease,” said Don Nicholson, Ph.D., Chief Executive Officer at Nimbus. “Furthermore, our preclinical data demonstrate that the effects of ACC inhibition extend to reducing inflammation and limiting fibrosis, which are hallmarks of NASH progression. We look forward to sharing these data with the scientific and medical community as we progress NDI-010976 through clinical development.”

NDI-010976 represents the first liver-targeted allosteric inhibitor of ACC intended for the treatment of NASH, an increasingly common, serious liver disease which is estimated to affect 16 million Americans.¹ NASH can lead to liver cirrhosis, often resulting in the need for a liver transplant, as well as other complications including hepatocellular carcinoma (HCC), a liver cancer with high mortality rates. Currently there are no therapies specifically approved to treat NASH, and limited options for patients with advanced HCC, and there are no other ACC inhibitors publicly disclosed to be in development for these diseases. In addition to NDI-010976, Nimbus is continuing to advance a pipeline of novel small molecules, including those for IRAK4, Tyk2, KRas and other medically important targets. 

¹Frontline Gastroenterol. 2014 Jul; 5(3): 211-218; Aliment Pharmacol Ther. 2011 Aug; 34(3): 274-85; World J Transplant. 2014 Jun 24; 4(2): 81-92; Hematology. 2014 Dec 29

Upcoming Poster Presentations

American Association of Cancer Research (AACR) Annual Meeting
April 18 – 22, 2015; Philadelphia, Penn.
Poster Title: Liver selective acetyl-CoA carboxylase inhibition by ND-654 improves survival in cirrhotic rats with hepatocellular carcinoma
Presentation Date and Time: Tuesday, April 21, 2015; 1:00 – 5:00 p.m. ET
Abstract #4452, Section 30, Poster Board #9

Nimbus, in collaboration with researchers from Massachusetts General Hospital, previously presented data (PDF File) demonstrating that daily oral administration of its ACC inhibitor ND-654 reduced tumor incidence by 55 percent in an animal model of cirrhosis and HCC. At today’s poster session, the researchers will present data showing that ND-654 significantly improved median survival time in this model, decreased tumor cell proliferation, induced tumor necrosis and decreased fibrosis. 

European Association for the Study of the Liver (EASL) 50th International Liver Congress 2015
April 22 – 26, 2015; Vienna, Austria
Poster Title: Liver-directed allosteric inhibitors of acetyl-CoA carboxylase favorably impact pathophysiology in the progression from NAFLD to NASH and Hepatocellular Carcinoma, including hepatic steatosis, inflammation, and fibrosis
Presentation Date and Time: Saturday, April 25, 2015; 3:30 – 4:00 p.m. CET
Poster Viewing: Saturday, April 25, 2015; 4:00 – 6:00 p.m. CET
Poster #LP-30

Note: The full abstract will be made available on the conference website at 7 a.m. CET on the day of the presentation.

About ACC and NASH

Acetyl CoA Carboxylase (ACC), a master regulator of fatty acid synthesis and oxidation, has been a sought-after, yet intractable target over the past two decades. Successful inhibition of ACC may enable new strategies to reduce lipids, inflammation, fibrosis, blood glucose, weight and cardiovascular risk. Nimbus is the first company to successfully design drug-quality allosteric inhibitors targeting ACC for the treatment of metabolic disease as well as cancer.

The company’s first indication for ACC-focused clinical development in metabolic disease is Non-alcoholic Steatohepatitis, or NASH, a serious condition that can lead to liver cirrhosis, often leading to transplant, and other complications including hepatocellular carcinoma (liver cancer). Currently there are no therapies specifically approved to treat NASH. Other possible metabolic disease indications for ACC inhibition include type 2 diabetes and hypertriglyceridemia.

About Nimbus

Nimbus Therapeutics harnesses the power of computational chemistry to design breakthroughs for the treatment of substantial and underserved human diseases. The company’s focus on metabolic diseases, cancer and immune-inflammatory disorders is driven by its selection of well validated targets that have proven intractable to the approaches taken by others in the pharmaceutical and biotechnology industry. Using its unique approach and technological capabilities, Nimbus is rapidly progressing highly selective and potent small molecules through discovery and development. The company’s advanced programs include ACC, IRAK4 and Tyk2. Nimbus is headquartered in Cambridge, Massachusetts (USA). To learn more, please visit www.nimbustx.com.

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Pfizer Venture Investments and Lightstone Ventures join existing investor syndicate; 
Company will enter clinical stage in 2015 with first ACC Inhibitor for NASH

CAMBRIDGE, Mass. – March 18, 2015 – Nimbus Therapeutics, a biotechnology company focused on designing highly selective and potent medicines to disrupt known drivers of serious diseases, today announced the successful completion of an oversubscribed $43 million Series B financing led by Pfizer Venture Investments and Lightstone Ventures. All of the company’s Series A investors, including Atlas Venture, SR One, Lilly Ventures and Bill Gates, also participated in the Series B round. Coinciding with this announcement, the company recently changed its name from “Nimbus Discovery” to “Nimbus Therapeutics,” to signal its transition to a clinical stage company.

“Our ability to attract such a high-caliber cadre of new and existing investors reinforces our belief in the boundless potential of our novel computational technology-driven approach to drug discovery and development,” said Donald “Don” Nicholson, Ph.D., chief executive officer at Nimbus. “This financing round sets the foundational stage for several key inflection points for Nimbus in 2015 and beyond. Progressing the first of our pipeline of small molecules into the clinic, we hope to make substantial strides this year toward realizing our mission to turn historically difficult targets into medicines that matter for patients.”

Nimbus plans to use the funds from the Series B round to advance its lead program, an Acetyl CoA Carboxylase (ACC) inhibitor, into clinical development, representing the first allosteric and liver-targeted inhibitor intended for the treatment of Non-alcoholic Steatohepatitis, or NASH, an increasingly common liver disease which is estimated to affect 16 million Americans.¹ Nimbus plans to report Phase 1 data from this program later this year. Additionally, the company will continue to advance its preclinical programs of novel small molecules including those for IRAK4, Tyk2, KRas and other medically-important targets.

“It’s clear that Nimbus not only is employing a breakthrough technological approach for drug discovery and development, but also has the scientific expertise and management acumen to translate the company’s vision into reality,” said Chris Christoffersen, Ph.D., General Partner, Lightstone Ventures. “We look forward to supporting Nimbus in the critical years ahead as it advances its promising therapeutics for people impacted by NASH and a broad spectrum of diseases with high unmet needs, and expands its potential reach and impact through new collaborations and partnerships.”

Nimbus’ programs address well-validated biological mechanisms implicated in areas of metabolic disease, cancer and immune-inflammatory disorders, which have proven intractable by traditional drug discovery methods. Employing a novel approach to research and development, Nimbus deeply integrates computer-driven drug design, chemistry and pharmacology, working in close coordination with its co-founding partner, Schrödinger, and a highly integrated network of partners and collaborators. The company has demonstrated the ability to accelerate discovery, design and optimization of drug candidates and rapidly move investigational medicines into the clinic. 

¹Frontline Gastroenterol. 2014 Jul; 5(3): 211-218; Aliment Pharmacol Ther. 2011 Aug; 34(3): 274-85; World J Transplant. 2014 Jun 24; 4(2): 81-92; Hematology. 2014 Dec 29

About ACC and NASH

Acetyl CoA Carboxylase (ACC), a master regulator of fatty acid synthesis and oxidation, has been a sought-after, yet intractable target over the past two decades. Successful inhibition of ACC may enable new strategies to reduce lipids, blood glucose, weight and cardiovascular risk. Nimbus is the first company to successfully design drug-quality allosteric inhibitors targeting ACC for the treatment of metabolic disease as well as cancer.

The company’s first indication for ACC-focused clinical development in metabolic disease is Non-alcoholic Steatohepatitis, or NASH, a serious condition that can lead to liver cirrhosis, often leading to transplant, and other complications including hepatocellular carcinoma, a liver cancer with high mortality rates. Currently there are no therapies specifically approved to treat NASH. Other possible metabolic disease indications for ACC inhibition include type 2 diabetes and hypertriglyceridemia.

About Nimbus

Nimbus Therapeutics harnesses the power of computational chemistry to design breakthroughs for the treatment of substantial and underserved human diseases. The company’s focus on metabolic diseases, cancer and immune-inflammatory disorders is driven by its selection of well validated targets that have proven intractable to the approaches taken by others in the pharmaceutical and biotechnology industry. Using its unique approach and technological capabilities, Nimbus is rapidly progressing highly selective and potent small molecules through discovery and development. The company’s advanced programs include ACC, IRAK4, and Tyk2. Nimbus is headquartered in Cambridge, Massachusetts (USA). To learn more, please visit www.nimbustx.com.

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Novel, broad-spectrum fungicides show compelling activity in initial crop field trials

CAMBRIDGE, Mass. and ST. Louis, Mo. – December 10, 2014 – Nimbus Discovery, a biotechnology company discovering novel approaches for previously inaccessible disease targets, and Monsanto Company, today announced the achievement of the first milestone in their research collaboration. The research collaboration, which was announced last year, focuses on the development of new discoveries to help farmers control diseases and promote overall plant health.

Under the collaboration, Nimbus and Monsanto are co-developing agricultural fungicides using Nimbus’ innovative research tools and Monsanto’s agricultural testing capabilities. With today’s announcement, Monsanto will make an undisclosed payment to Nimbus based on the demonstration of activity of novel, broad-spectrum fungicides in key crops of interest.

Growers around the world are continuously searching for new tools to help them control fungal infestations which impact their harvest on farms. Today, it is estimated that fungal infestations reduce global yields 13 percent on average despite the use of resistant crop varieties and the approximately $14 billion that is spent annually on fungicide treatments.

Fungal infections appear as rusts, leaf spots, mildews and blights on a range of important crops. Novel fungicides would provide growers with additional tools to prevent yield loss, as well as combat emerging resistance to existing fungicide treatments or applications.

Under the terms of the agreement, a jointly-owned entity has been created that has access to Nimbus’ validated computational and molecular-evolution platform. Monsanto has rights to applications within agriculture and Nimbus will retain rights for all other applications.

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, 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.

About Monsanto

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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Key hire bolsters partnering and financing efforts

CAMBRIDGE, Mass. – November 4, 2014 – Nimbus Discovery LLC, a biotechnology company discovering novel medicines against important, but previously inaccessible drug targets, today announced the appointment of Jeb Keiper as Chief Business Officer. In this role, Mr. Keiper is responsible for structuring, negotiating and executing successful strategic alliances, co-development agreements, and financial investments, as well as providing management and strategic leadership to the organization. Mr. Keiper takes over the reins as Chief Business Officer from Jonathan Montagu, who remains a key contributor for Nimbus Discovery, and who is now based out of Europe.

Mr. Keiper brings over 15 years of experience in pharmaceutical and biotech companies and was previously the Vice President of Business Development for GSK Oncology. In this role, he was responsible for identifying and concluding several critical collaborations for GSK in Oncology, including his leadership of the $16B Novartis-GSK Oncology integration. Prior to GSK, Mr. Keiper held positions in business development with multiple companies and served as a consultant at McKinsey & Company, after having started his career as a pharmaceutical chemist.

Don Nicholson, Chief Executive Officer of Nimbus Discovery, said: “It is a great pleasure to welcome Jeb to our management team at Nimbus. Jeb brings valuable corporate development skills, leadership experience, and relationships across the industry. He joins at a transformational time for Nimbus Discovery as our lead program, the first allosteric inhibitor of acetyl-CoA carboxylase (ACC), enters patients in early 2015. Jeb will be instrumental as we intensify our partnering and financing efforts to further advance our broad pipeline in oncology, immunology and metabolic disorders, and continue to build on the success of our platform.”

Mr. Keiper holds four degrees from the Massachusetts Institute of Technology (MIT); one in Chemistry, two in Chemical Engineering, and an M.B.A. from the MIT Sloan School of Management with joint program in Biomedical Enterprises with the Harvard Medical School.

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.

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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.

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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.

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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.

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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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