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Frontier Pharma:抗生素 - First-in-Class的革新認識和商業化

Frontier Pharma: Antibiotics - Identifying and Commercializing First-in-Class Innovation

出版商 GBI Research 商品編碼 326288
出版日期 內容資訊 英文 91 Pages
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Frontier Pharma:抗生素 - First-in-Class的革新認識和商業化 Frontier Pharma: Antibiotics - Identifying and Commercializing First-in-Class Innovation
出版日期: 2014年12月31日 內容資訊: 英文 91 Pages



抗生素的開發平台非常活躍,741個產品正在開發。其中大多數 (85%) 在前臨床階段,還沒參加臨床試驗。


第1章 目錄

第2章 摘要整理

第3章 革新 (技術創新) 案例

  • 分子標靶多樣化
  • 生技藥品的機會擴大
  • 創新的First-in-Class產品 (劃時代的醫藥品) 的開發現在也富有魅力
  • 法規、償付政策,對First-in-Class產品的革新有利
  • 褒獎金
  • 報告指南

第4章 臨床、商業性情形

  • 病因
  • 病理生理學
  • 傳統抗生素的開發與相關的作用機制
  • 抗生素抗性的機制
  • 治療流程
  • 未來的抗生素開發

第5章 開發中產品革新的評估

  • 抗生素開發平台:各階段、分子類型、分子標靶
  • 抗生素開發平台:各作用機制
  • 新分子標靶的First-in-Class開發平台計劃

第6章 First-in-Class標靶評估

第7章 專利申請

第8章 交易與策略性整合

  • 產業整體的First-in-Class交易
  • 交易形勢
  • 許可證交易
  • 共同開發交易
  • 不參與許可/共同開發交易的First-in-Class計劃

第9章 附錄


Product Code: GBIHC353MR

Executive Summary

An Extensive Developmental Pipeline, but Limited First in Class Innovation

The antibiotics pipeline is very active, with 741 products in development. Of these, the majority (85%) are at the Discovery or Preclinical stages and have not yet entered human trials. Such a high proportion of drugs at the earliest stages of development would, in other indications, provide hope of a steady stream of drugs due to advance through the stages of development and be approved within the next decade. However, the development of antibiotics, particularly the progression of drug candidates from Discovery to human trials, is notoriously difficult, with only 12 new antibiotics approved since 2000. Of these pipeline drugs, the distribution of molecular targets is very limited, with the majority having targets observed among marketed products.

Reflecting this trend is the fact that despite the large pipeline, first-in-class drug development is minimal, with only 10% of pipeline drugs acting on a first-in-class target. This distribution reflects the pipeline, in which 85% is at either Discovery or Preclinical. Three first-in-class drugs are at Phase I, eight are at Phase II, but none are at Phase III. These 75 drugs act on 38 first-in-class targets.

Diversity is low among these 38 targets, of which 21, acted upon by 39 products, have mechanisms of action that can be classified under the broad modes of action common to established classes of antibiotics. One of the most common is protein synthesis inhibitors, under which eight first-in-class targets can be grouped. Other categories include RNA and DNA synthesis inhibitors, as well as bacterial cell wall and membrane disruptors. Of the drugs targeting first-in-targets, clinical trial data regarding their safety and efficacy are limited, with the majority of drugs being at either the Discovery or Preclinical stages of development. As such, firm conclusions can only be drawn on a select number of targets. Those with the most promising results include inhibitors of UDP2 epimerase, Methionine tRNA synthase, the FtsZ proteins, and NDM-1 beta lactamase.

Many of the targets under these categories were highlighted by research into conserved genomes of bacteria, driven by a desire to generate antibiotics with as broad a spectrum of use as possible. These studies have uncovered a plethora of targets that act upon mechanisms not yet utilized in the treatment of bacterial infection. It was hoped that high-throughput screens against these targets would lead to the development of novel classes of antibiotics; however, since the 1990s, only four new classes of antibiotics have been approved. With the failure of the genomic approach and the fact that the natural sources of many bacteria are thought to be exhausted, many companies have left the field altogether. However, incentives to draw pharma back to the field, and methods of improving success with compound searches, as outlined in this report, provide hope for the future.

A Moderate Number of Deals and Strategic Consolidations, but Little Interest in First-in-Class Products

Deals involving antibiotics are common, with 266 conducted from 2006-2014. Of these, the majority were licensing deals (64%), with 46% conducted once the product was marketed. This reflects the fact that drug development in antibiotics is relatively simple and has easy-to-assess endpoints, reducing the requirement of co-development deals to develop an antibiotic successfully once a strong lead candidate has been identified.

Deal values varied widely from $4.3m to $480m, but most were below $100m. Only 19% of deals were completed before the drug entered human trials, again supporting the theory that drug development in antibiotics does not require significant investment.

Reflective of the lack of first-in-class targets in the developmental pipeline, only six deals involve drugs against first-in-class targets. Two deals were conducted at Phase I, two at Phase II and one at an undisclosed Phase. No robust trends can be drawn from such limited data. However, with all disclosed deals conducted after the drug has entered human trials, it can be speculated that the historic trend in the failure of identified chemicals to translate into lead compounds strongly deters potential investors from investing in first-in-class compounds. With few first-in-class compounds in the current developmental pipeline, 80% of which are at Discovery or Preclinical, few deals involving first-in-class drugs are expected to be announced within the next few years.


The report covers and provides -

  • A brief introduction to antibiotics, including profiles of clinically relevant infectious strains, bacteria virulence, and an overview of pharmacotherapy
  • Highlights of the changing molecular target landscape between market and pipeline, focusing on points of innovation
  • An overview of how innovation products are contributing to the pipeline and market for antibiotics
  • A comprehensive review of the pipeline for first-in-class therapies, analyzed on the basis of Phase distribution, molecule type, molecular target, and route of administration
  • Identification and assessment of first-in-class molecular targets with a particular focus on early-stage programs of which clinical utility has yet to be evaluated, as well as literature reviews of novel molecular targets
  • Assessment of the licensing and co-development deals for antibiotic therapies

Reasons to buy

  • The report provides the following -
  • Understanding of the overall focal shifts in the molecular targets in the antibiotics pipeline
  • Understand of the distribution of pipeline programs by Phase of development, molecule type and molecular target
  • Scientific and clinical analysis of first-in-class developmental programs
  • Assessment of the valuations of licensed and co-developed antibiotic treatments
  • A list of first-in-class therapies potentially open to deal-making opportunities
  • Analysis of financial valuations on licensed or co-developed first-in-class therapies and generics

Table of Contents

1. Table of Contents

  • 1.1. List of Tables
  • 1.2. List of Figures

2. Executive Summary

  • 2.1. A Low Degree of First-in-Class Innovation in a Very Active Pipeline
  • 2.2. A low Diversity in the Mechanisms of Action of First-in Class Targets
  • 2.3. A High Number of Deals Involving Antibiotics, but Few involving First-in-Class Targets

3. The Case for Innovation in Antibiotic Development

  • 3.1. Diversification of Molecular Targets
  • 3.2. Growing Opportunities for Biological Products
  • 3.3. Innovative First-in-Class Product Developments Remain Attractive
  • 3.4. Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation
  • 3.5. Financial Incentives
  • 3.6. Report Guidance

4. Clinical and Commercial Landscape

  • 4.1. Etiology
    • 4.1.1. Adherence to Host Cells and Biofilm Formation
    • 4.1.2. Toxins and Toxin Secretion Systems
    • 4.1.3. Ability to Evade the Host Immune System
  • 4.2. Pathophysiology
  • 4.3. Traditional Antibiotic Development and Associated Mechanisms of Action
    • 4.3.1. Overview
    • 4.3.2. DNA Synthesis and Transcription Machinery
    • 4.3.3. RNA Synthesis Arrest
    • 4.3.4. Disruption of Cell Wall Stability of Formation
    • 4.3.5. Disruption of Cell Membrane Formation and Stability
    • 4.3.6. Disruption of Cell Metabolism
    • 4.3.7. Inhibition of Protein Synthesis
  • 4.4. Mechanisms of Antibiotic Resistance
    • 4.4.1. Target Modification
    • 4.4.2. Efflux Pumps
    • 4.4.3. Enzymatic Inactivation of Antibiotics
    • 4.4.4. Changes to Outer Membrane Permeability
  • 4.5. Treatment Algorithm
  • 4.6. The Future of Antibiotic Development

5. Assessment of Pipeline Product Innovation

  • 5.1. Antibiotic Pipeline by Phase, Molecule Type and Molecular Target
  • 5.2. Antibiotic Pipeline by Mechanism of Action
  • 5.3. First-in-Class Pipeline Programs Targeting Novel Molecular Targets

6. First-in-Class Target Evaluation

  • 6.1. Pipeline Programs which Target Lipoteichoic Acid or Lipoteichoic Acid Synthase
  • 6.2. Pipeline Programs which Target Pseudomonas Aeruginosa Lectins LecA and LecB
  • 6.3. Pipeline Programs which Target Sortase A
  • 6.4. Pipeline Programs which Target Pyruvate Kinase
  • 6.5. Pipeline Programs which Target UDP-N-acetylglucosamine 2-epimerase
  • 6.6. Pipeline Programs which Target Peptide Deformylase
  • 6.7. Pipeline Programs which Target LpxC enzyme
  • 6.8. Pipeline Programs which Target Sialic Acid Transporter TRAP
  • 6.9. Pipeline Programs which Target Methionine tRNA Ligase
  • 6.10. Pipeline Programs which Target FtsZ Protein
  • 6.11. Pipeline Programs which Target Clostridium Difficile Toxins A and B
  • 6.12. Pipeline Programs which Target Staphylococcus Enterotoxins A and B
  • 6.13. Pipeline Programs which Target NDM-1 Beta Lactamase
  • 6.14. Pipeline Programs which Target DegS Serine Endoprotease
  • 6.15. Pipeline Programs which Target A Disintegrin and Metalloproteinase 10
  • 6.16. Pipeline Programs which Target Translocase-1

7. Patent Filings

8. Deals and Strategic Consolidations

  • 8.1. Industry Wide First-in Class Deals
  • 8.2. Antibiotics Deals Landscape
  • 8.3. Licensing Deals
    • 8.3.1. Molecule Type and Mechanism of Action
  • 8.4. Co-Development Deals
    • 8.4.1. Molecule Type and Mechanism of Action
  • 8.5. First-in-Class Programs Not Involved in Licensing or Co-Development Deals

9. Appendix

  • 9.1. Abbreviations
  • 9.2. References
  • 9.3. Contact Us
  • 9.4. Disclaimer

List of Tables

  • Table 1: Market for Antibiotics, Global, Bacterial Species Specifically Mentioned in Chemical Entity Patent Families, (2003-2012)
  • Table 2: Organizations Frequently Applying for Antibiotic Chemical Entity Patent Families, 2003-2012
  • Table 3: Abbreviations

List of Figures

  • Figure 1: Sales Performance of First-in-Class and Non-First-in-Class Product post-Marketing Approval
  • Figure 2: Marketed Products by Mechanism of Action
  • Figure 3: Treatment, Development and Resistance and Mechanisms of Resistance Across Different Bacterial Species
  • Figure 4: Conserved Bacterial Molecular Targets
  • Figure 5: Pipeline Overview
  • Figure 6: Developmental Pipeline by Mechanism of Action
  • Figure 7: Molecular Target Category Comparison, Pipeline and Marketed Products
  • Figure 8: Molecular Target Category Comparison for Traditional Antibiotics, Pipeline and Marketed Products
  • Figure 9: First-in-Class and Non-First-in-Class Pipeline Product Comparison
  • Figure 10: Market for Antibiotics, Global, Developmental Pipeline, 2014
  • Figure 11: LTA and LTA Synthase as Therapeutic Targets
  • Figure 12: Pipeline Programs Targeting LTA and LTA Synthase
  • Figure 13: LecA and LecB as Therapeutic Targets
  • Figure 14: Pipeline Programs Targeting Pseudomonas Aeruginosa Lectins LecA and LecB
  • Figure 15: Sortase A as a Therapeutic Target
  • Figure 16: Pipeline Programs Targeting Sortase A
  • Figure 17: Pyruvate Kinase as a Therapeutic Target
  • Figure 18: Pipeline Programs Targeting Pyruvate Kinase
  • Figure 19: UDP-N-acetylglucosamine 2-epimerase as a Therapeutic Target
  • Figure 20: Pipeline Programs Targeting UDP-N-acetylglucosamine 2-epimerase
  • Figure 21: Peptide Deformylase as a Therapeutic Target
  • Figure 22: Pipeline Programs Targeting Peptide Deformylase
  • Figure 23: LpxC enzyme as a Therapeutic Target
  • Figure 24: Pipeline Programs Targeting LpxC Enzyme
  • Figure 25: Sialic Acid Transporter TRAP as a Therapeutic Target
  • Figure 26: Pipeline Programs Targeting Sialic Acid Transporter TRAP
  • Figure 27: Methionine tRNA Ligase as a Therapeutic Target
  • Figure 28: Pipeline Programs Targeting Methionine tRNA Ligase
  • Figure 29: FtsZ Protein as a Therapeutic Target
  • Figure 30: Pipeline Programs Targeting FtsZ Protein
  • Figure 31: TcdA and TcdB as Therapeutic Targets
  • Figure 32: Pipeline Programs Targeting TcdA and TcdB
  • Figure 33: SEA and SEB as Therapeutic Targets
  • Figure 34: Pipeline Programs Targeting SEA and SEB
  • Figure 35: NDM-1 Beta Lactamase as a Therapeutic Target
  • Figure 36: Pipeline Programs Targeting NDM-1 Beta Lactamase
  • Figure 37: DegS Serine Endoprotease as a Therapeutic Target
  • Figure 38: Pipeline Programs Targeting DegS Serine Endoprotease
  • Figure 39: A Disintegrin and Metalloproteinase 10 as a Therapeutic Target
  • Figure 40: Pipeline Programs Targeting A Disintegrin and Metalloproteinase 10
  • Figure 41: Translocase-1 as a Therapeutic Target
  • Figure 42: Pipeline Programs Targeting Translocase-1
  • Figure 43: Chemical Entity Patent Families Filed and Granted for Antibiotics, Global, 2003-2012
  • Figure 44: Industry-Wide Deals by Stage of Development, 2006-2014
  • Figure 45: Industry Licensing Deal Values by Stage of Development, 2006-2014
  • Figure 46: Licensing Deals, Geographic Distribution, 2006-2014
  • Figure 47: Licensing Deals, 2006-2014
  • Figure 48: Licensing Deals Analysis, 2006-2014
  • Figure 49: Licensing Deals, 2006-2014 - Part 1
  • Figure 50: Licensing Deals, 2006-2014 - Part 2
  • Figure 51: Co-Development Deals, Geographic Distribution, 2006-2014
  • Figure 52: Co-Development Deal Value Analysis, 2006-2014
  • Figure 53: Co-Development Deals Analysis, 2006-2014
  • Figure 54: Developmental Pipeline, 2014 - Part 1
  • Figure 55: Developmental Pipeline, 2014 - Part 2
  • Figure 56: Market for Antibiotics, First-in-class Programs with no Recorded Prior Deal Involvement, 2006-2014
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