Whitepaper: Re-Opening the Pharmaceutical Pipeline with First in class Drug Leads

8/9/2019 Whitepaper: Re-Opening the Pharmaceutical Pipeline with First in class Drug Leads

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ODIN Industries 100 Snapfinger Drive Athens, GA 30605 706.540.7325 ODINIndustries.com

From Art to Engineering: Re-Opening the Pipeline with

Innovative New and Late Stage Drug Leads

Abstract

The pharmaceutical industry is being squeezed by a drug development process that is slowing

the flow of new products through the pipeline. As a result, there is a tremendous backlog of

best-in-class new and late stage drug leads that are being discovered more quickly than the

pharmaceutical industry can develop them. Thus, at time when they are needed most, some of

the industrys most valuable leads remain unexploited and under explored. There is, however,

tremendous opportunity in this backlog of challenging but active molecules. The development of

an advanced platform technology that can reduce the time and cost to bring these new products

to market can re-energize the pharmaceutical industry, and propel it decades into the future.

From Where Will the Next Blockbusters Come?

There is a deep sense of anxiety in both the financial and healthcare sectors given the current

state of the pharmaceutical industry. At a time when high profile drug classes are being

withdrawn, patent protection is expiring and pharmaceutical companies are pinning their

financial health on second and third generation me too medicines, never has so money much

been spent on research and development with so little result.

Companies are taking longer than ever to bring products to market, and periods of marketexclusivity are diminishing rapidly. Even after a medicine is discovered teams of engineers,

biologists, chemists and physicists must spend long hours figuring out how to mass produce the

results achieved by an individual scientist at the lab bench. Often promising experiments are not

replicable on a large scale - the reaction may give off extreme heat, or cause an explosion, or

release a toxic gas. The research may fail because it is not possible to manufacture the drug

safely or to the proper specifications.

More importantly, in an industry where new product pipelines are everything, there are notenough drugs in the piepeline. Investigational new drug applications have decreased alarminglyover the last decade, and the expanding role of biotechnology has introduced even more

uncertainty into the industry. When one biologic drug can cost a patient as much as $25,000 peryear, how many drugs of this type can a patient afford or will the health care system absorb?

The era of new, high-margin small molecule drugs is quickly vanishing, and pharmaceuticalcompanies are looking for ways to maintain a constant flow of new products. Traditional smallmolecule drugs will undoubtedly remain part of the industrys focus, as will large molecules andthe continued expansion into biotech. The question is Will these developments provide a strongenough platform to sustain the industrys growth?


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Macrocycles: The Next Generation of Blockbusters

Pharmaceutical companies, academic institutions and research organizations have discoveredcountless molecules that are ready to be developed, but are substantially more expensive to movethrough the pipeline with current research and development methods. These formulas are

subsequently relegated to the file cabinets, which results in the postponement of new drugs untila new, less expensive means of development is discovered.

These drug leads, collectively referred to as macrocycles, are a particularly rich source of noveldrug candidates that combine the potency and selectivity of large molecules with the preferredproperties of small molecules. Although some scientists may challenge the assertion thatmacrocycles make better drugs than both small and large molecules, the data is overwhelming.Molecules in nature are often brought to a bioactive conformation by ring formation(macrocyclization).

Macrocycles are small to medium sized natural, semi-natural, or artificial molecules where the

atoms are connected in a fashion such that they form a ring. These molecules occupy the vastarea of chemical space that lies between small molecules and large molecules, but have beenlargely unexploited due to the difficulties associated with their synthesis. Until now,methodologies for producing macrocycles required years of work, produced large amounts oftoxic waste, required large and expensive manufacturing facilities, and yet still produced verylow yields of the desired material.

Despite these past difficulties, however, a great deal of research is still conducted usingmacrocycles. The cyclic structure of these molecules make them particularly attractive drugtargets since it protects them from destruction by the human body, and increases theireffectiveness compared with their linear analogs by constraining it to an active form.

A recent Harvard study demonstrated that cyclization of biologically-active linear

compounds increased the specificity of responses and was the DOMINANT factor

in global activity patterns. As a result, the potential for creating blockbuster leads

from macrocycles is enormous, where hit rates in some macrocyclic libraries are

as high as 1 in 100, very much better than is seen in small molecule libraries where

the figure is closer to 1 in 10,000.

Ready access to these molecules will energize an industry that is starved for new products -enabling companies to quickly expand their product pipeline with cutting-edge, first-in-classpharmaceuticals, and accelerate research on pioneering pharmaceuticals that would not otherwisebe viable for many years into the future.

So Why Dont More Macrocycles Make it to Market?

Naturally-occurring macrocycles are highly evolved, highly specific, and can be highly effectivetoward the gene products with which they coevolved. And for more than 50 years thesemacrocycles have been a wellspring of drugs and drug leads, serving as the inspiration for nearly


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every new drug class introduced by the pharmaceutical industry. Industry icons such as Insulin,FK-506, Taxol, and Vancomycin are all macrocycles.

Accordingly, macrocycles constitute a major class of pharmaceutical agents currently under pre-clinical and clinical investigation for the treatment of virtually every disease. Furthermore,

macrocycles are key components in drug delivery and diagnostic technologies.

Notwithstanding their long history as lead compounds, very few intact macrocycles make it tomarket. This difficulty is NOT due to a small number of promising leads. Quite the contrary,over the past decade, the number of macrocycles has increased in an explosive manner. In fact,the macrocyclic structure is arguably the most diverse structure found in nature.

Paradoxically, the cyclic nature of this class of molecules has made it notoriously difficult andexpensive to obtain them in sufficient quantities the poster-child for the challenges associatedwith bringing scientific discoveries from the laboratory to the marketplace . While some of thesecompounds are available from biological sources in quantities sufficient for basic research or

initial clinical studies, others need to be produced by semi- or total synthesis. And unfortunately,the constant incremental improvement of biological and synthetic methods available to thepharmaceutical industry has not kept pace with the level of complexity found in the industrysmost promising lead compounds.

Thus, regardless of the overwhelming clinical success of macrocycles, many valuable leads havebeen abandoned in late stages of development OR were marketed as less potent linear analogs.

Unfortunately for the pharmaceutical industry, stockholders and patients, these linear analogsrarely if ever achieve the therapeutic benchmark established by their cyclic ancestors. Thus, thestaggering potential of macrocyclic research and development is largely unrealized as the resultof the inability of the art to provide a practical method for making such compounds.

ODIN Industries Provides the Key to Macrocycle Research and Development

ODIN Industries is a molecular engineering company that has developed an advanced platformtechnology for the preparation of macrocyclic compounds. This is a timely solution that expandsthe range of innovative new molecular entities that are accessible to the pharmaceutical industry.

ODINs new high concentration synthetic process dramatically simplifies the preparation ofmany new and late-stage drug leads by using robust proprietary methods with high selectivity forthe desired product. This allows pharmaceutical companies to cost-effectively movemacrocycles from their drug discovery programs to the marketplace. This is a significantachievement, since the necessity of obtaining even gram quantities of these molecules has beenthe major stumbling block in their development.

Some of the unique features and benefits of ODINs technology include:

Versatile methods that will enable the preparation of all important macrocycles using compactsynthetic schemes, so that no useful compound is inaccessible to practical synthesis


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Synthetic procedures that can be varied systematically for the purpose of optimizing specificproperties of the reaction products

Efficient methods that not only produce small samples of the new material, but are suitable forlarge scale manufacturing so that entirely new synthetic schemes DO NOT need to be invented

Efficient processes such that compact chemical plants can make required amounts of productefficiently, safely, and with minimal environmental impact

The bottom line is this ODINs technology gives the pharmaceutical industry the ability toexploit vast, undeveloped chemical space, re-establish strong patent protection, and deliver bigmargins on molecules that have had small or no profit margins.

Best of all, ODINs technology can be operational in research laboratories throughout the worldwithin months, integrated into existing facilities without the need for additional infrastructure ora new brain trust.

About ODIN Industries

ODIN Industries is a leading molecular engineering company specialized in macrocycle R&D,technology assessment, and pharmaceutical pipeline development. The companys proprietarytechnology gives companies the ability to exploit vast, undeveloped chemical space, re-establishstrong patent protection, and deliver big profit margins on molecules that have had little or nocommercial viability. Through internal and external programs, licensing, and partnerships,ODIN is working to drive the discovery and development of new diagnostics, therapeutics andother macrocycle-based technologies.

For more information contact John R. Cool, ODIN Marketing & Communications, at (612) 332-767 or at [email protected].

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Whitepaper: Re-Opening the Pharmaceutical Pipeline with First in class Drug Leads