New to Insight Pharma Reports is a report on Macrocycles: Discovery and Development, Company Profiles, and Technologies.

This report covers several areas of macrocycles, specifically in technology and current research in development. With background the first four chapters including background material, this report covers what macrocycles are and the pharmacokinetic properties (absorption, distribution, metabolism, and excretion) they experience. Challenges with these molecules (including plasma concentrations, drug-drug interactions, and drug dose administrations) are also covered. Chapter 3 expands upon other properties that are considered with drug development, specifically cell permeability oral bioavailability, and drug absorption design. Chapter 4 ties all the ends with why macrocycles are being studied and what makes them stand out compared to other drug classes. Additionally, Chapter 4 also includes a survey conducted by Insight Pharma Reports. WIth over 90 participants, questions included familiarity with macrocycles, use in research, and challenges encountered.

Chapters 5-13 detail various companies and their strategies for studying macrocycles as drug candidates. Starting out with background material, Insight Pharma Reports has received the participation of:
• Bicycle Therapeutics
• Encycle Therapeutics
• Ensemble Therapeutics
• Lanthio Pharma
• Oncodesign
• Pepscan
• PeptiDream
• RA Pharmaceuticals
• Tranzyme Pharmaceuticals

Included with each section are detailed descriptions of company overviews, technology platforms, benefits, challenges, competitive advantage, partnerships and future aspirations. Also provided are exclusive interviews at the end of each section.

Table Of Contents

Table of Contents

Executive Summary

Chapter 1: What are macrocycles?

1.1 Background

Chapter 2: What are pharmacokinetic properties?

2.1 Absorption
2.2 Distribution
2.3 Metabolism
2.4 Excretion
2.5 Challenges in reaching pharmacokinetic requirements
2.5.1 Plasma concentrations
2.5.2 Drug-drug interactions
2.5.3 Drug dose administration

Chapter 3: What are other properties to consideration in drug development?

3.1 Cell permeability
3.2 Drug absorption design
3.3 Oral bioavailability

Chapter 4: Why Macrocycles?

4.1 Pharmacokinetic properties of macrocycles
4.2 Cell permeability properties
4.3 Protein-protein interactions
4.4 Higher binding affinity
4.5 Improved binding modes
4.6 Therapeutic applications
4.7 Challenges to macrocycles in drug discovery
4.8 Who’s working with macrocycles?

Chapter 5: Bicycle Therapeutics

5.1 Company Background
5.2 Technology platform
5.3 Benefits
5.4 Challenges and areas of improvement
5.5 Partnerships and future aspirations
5.6 Interview with Rolf Guenther
5.6.1 Company background
5.6.2 Cyclization chemistry platform
5.6.3 Macrocyclic properties
5.6.4 Partnerships and future aspirations

Chapter 6: Encycle Therapeutics

6.1 Company background
6.2 Proprietary platform
6.3 Partnerships, competitive advantage, and future outlook
6.4 Interview with Andrew Roughton
6.4.1 Company background
6.4.2 Proprietary technology platform
6.4.3 Tracking and properties of macrocycles
6.4.4 Partnerships and future aspirations

Chapter 7: Ensemble therapeutics

7.1 Company Background
7.2 DNA-Programmed Chemistry Platform
7.3 Benefits to DNA Programmed Chemistry Platform
7.4 Challenges to DNA Programmed Chemistry Platform
7.5 Competitive advantage
7.6 Partnerships and future growth
7.7 Interview with Nick Terrett
7.7.1 Company background
7.7.2 Ensemble’s use of macrocycles
7.7.3 Creating macrocycles
7.7.4 Ensemble’s technology used for macrocyclic creations
7.7.5 Macrocyclic structures and expected interactions
7.7.6 Challenges and properties in macrocyclic development
7.7.7 Ensemble partnerships and future aspirations

Chapter 8: Lanthio Pharma

8.1 Company background
8.2 Bacterial technology platform
8.3 Benefits to Lactococcus lactis platform
8.4 Challenges encountered
8.5 Competitive advantage
8.6 Partnerships and future growth
8.7 Interview with Gert Moll
8.7.1 Company background
8.7.2 Lanthio Pharma’s technology used for cyclic peptide creations
8.7.3 Lanthio Pharma’s use of macrocycles and cyclic peptides
8.7.4 Cyclic peptides and expected interactions
8.7.5 Challenges and properties in cyclic peptide development
8.7.6 Lanthio Pharma’s competitive advantage
8.7.7 Lanthio Pharma partnerships and future aspirations

Chapter 9: Oncodesign Biotechnology

9.1 Company Background
9.2 Nanocyclix platform
9.3 Benefits of Nanocyclix molecules
9.4 Challenges encountered
9.5 Competitive advantage
9.6 Partnerships and future growth
9.7 Interview with Jan Hoflack
9.7.1 Company background
9.7.2 Technology used for nanocyclic creations
9.7.3 Oncodesign’s use of macrocycles
9.7.4 Nanocyclic structures and expected interactions
9.7.5 Oncodesign’s partnerships and future aspirations

Chapter 10: Pepscan Therapeutics

10.1 Company background
10.2 Chemical Linkage of Peptides onto Scaffolds (CLIPS) platform
10.3 Benefits of the CLIPS platform
10.4 Challenges of the CLIPS platform
10.5 Partnerships and future aspirations
10.6 Interview with Peter Timmerman
10.6.1 Macrocycle background
10.6.2 CLIPS platform
10.6.3 Macrocyclic properties
10.6.4 Partnerships, competitive advantage, and future aspirations

Chapter 11: PeptiDream Incorporation

11.1 Company background
11.2 Peptide Discovery Platform System (PDPS)
11.3 Challenges to PDPS and macrocyclic creations
11.4 Competitive advantage, partnerships, and future aspirations
11.5 Interview with Patrick Reid
11.5.1 Company background
11.5.2 PDPS platform
11.5.3 Macrocycle properties
11.5.4 Challenges encountered
11.5.5 Competitive advantage
11.5.6 Partnerships and future aspirations

Chapter 12: Ra Pharmaceuticals

12.1 Company background
12.2 Translation platform and macrocyclic creations
12.3 Challenges encountered
12.4 Competitive advantage, partnerships, and future aspirations
12.5 Interview with Doug Treco
12.5.1 Company background
12.5.2 Technology platform
12.5.3 Macrocycle tracking, creations, and properties
12.5.4 Challenges encountered
12.5.5 Partnerships and future aspirations

Chapter 13: Tranzyme Pharmaceuticals

13.1 Company background
13.2 Macrocyclic Template Chemistry (MATCH) platform
13.3 L and D stereochemistries
13.4 Benefits and competitive advantages
13.5 Challenges
13.6 Partnerships and future aspirations
13.7 Interview with Mark L. Peterson
13.7.1 Company background

Acronyms used in this report

References

About Cambridge Healthtech Institute



Figures:

Figure 1.1: Example of macrocycles
Figure 4.1: Organizations surveyed
Figure 4.2: Approximate amount of time spent studying macrocycles
Figure 4.3: Specific areas of study
Figure 4.4: Challenges encountered
Figure 5.1: Different peptide structures with the same amino acid sequence
Figure 6.1: Multicomponent Ugi reaction yields a hexapeptide constrained in a macrocycle
Figure 7.1: Hybridization of DNA synthesizes macrocycle compounds
Figure 8.1: Methyl-lanthionine formed by a thioether-bridge
Figure 8.2: Lanthipeptide library on Lactococcus lactis cell surface
Figure 10.1: Linear peptide vs. CLIPS-peptide

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