Why look to existing, approved drugs to tackle a complex disease like obesity?

At first glance, creating a completely new molecule might seem like the obvious route. However, repurposing existing drugs offers compelling strategic, financial, and regulatory advantages—advantages that drive the development of Energesis’ lead candidate, EGS-2632.

 

 

The Benefits of Drug Repurposing

 

1. Proven Safety and Tolerability Profiles

Developing new drugs is notoriously risky: roughly 30% of candidate molecules fail in clinical trials due to safety concerns. Previously approved drugs, by contrast, have already demonstrated safety and manageable side effects in human populations. While no drug is without side effects, using well-characterized compounds significantly reduces the risk of unexpected toxicity.

 

2.    Streamlined Regulatory Pathways – The 505(b)(2) Route

The U.S. FDA offers an expedited approval pathway known as 505(b)(2) for repurposed therapeutics. This process allows a company to rely on pre-existing clinical and scientific data — either from published literature or previous sponsor studies — rather than re-inventing the wheel. Avoiding redundant safety trials saves years of clinical development.

 

3. Substantial Cost Savings

Time in clinical development correlates directly with cost. By leveraging existing safety data and bypassing early-phase toxicity trials, repurposing can save tens of millions of dollars, depending on the target indication and trial scope.

 

 

How This Applies to EGS-2632

 

EGS-2632 is a fixed-dose combination of two drugs that have been marketed globally for decades with excellent safety track records.

While FDA regulations require drug combinations to demonstrate both individual safety and combined safety, our strategy relies on existing standalone data to fulfill the individual safety requirements. This allows us to focus our resources primarily on demonstrating the safety and efficacy of the combination itself.

 

 

Drug A (established safety)                    EGS-2632

                    +              →    (focused testing of the combination's

Drug B (established safety)             safety and efficacy)

 

True Synergistic Efficacy

 

Regulatory agencies require each component of a combination therapy to contribute meaningfully to its overall effect. Our preclinical models support this: neither drug alone approaches the weight-loss efficacy achieved by the combination.

Preclinical Disclaimer: Energesis' programs, including EGS-2632, are currently in preclinical development. They have been evaluated only in laboratory and animal models and have not yet been tested in humans. They are not approved by any regulatory authority, and preclinical results may not predict human safety or efficacy.

 

 

Overcoming Intellectual Property Misconceptions

 

A common critique of drug repurposing is that old molecules lack strong patent protection. Traditionally, the "gold standard" of pharmaceutical intellectual property is a composition-of-matter patent, which prevents competitors from commercializing the specific molecule.

However, repurposed combinations can qualify for this top-tier protection if they demonstrate unexpected, novel properties. For EGS-2632, preclinical studies revealed two critical findings:

 

     1. Low-Dose Efficacy: Significant weight loss is achieved even when each drug is administered at a fraction of its previously approved dose.
 

     2. True Synergy: The combined therapeutic effect is greater than the simple sum of its parts (1+1>2).
 

Based on these discoveries, the U.S. Patent and Trademark Office recently granted composition-of-matter patent claims for EGS-2632, alongside use claims for treating obesity and related metabolic conditions. These provide both composition-of-matter and use protection for our lead product candidate.

 

 

A Shifting Industry Landscape

 

Big Pharma’s perspective on drug repurposing has evolved substantially in the past few years. High capital costs, lengthening development timelines, and eroding patent windows for new chemical entities have driven a shift toward lower-risk, high-value assets.

A prominent example of this is Karuna Therapeutics. Karuna developed a combination of generic compounds to target symptoms of schizophrenia that traditional therapies failed to address. Backed by composition-of-matter patents and strong Phase 3 data in an area of high unmet need, Karuna was acquired by Bristol Myers Squibb for $14 billion.

 

 

The Bottom Line

 

In an era defined by escalating clinical trial costs, EGS-2632 combines the reduced risk profile of proven therapeutics with robust patent protection and clear synergistic efficacy — positioning it as a compelling candidate in the treatment of obesity.

 

 

Sources

1.        Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm Sin B. 2022 Jul;12(7):3049-3062. doi: 10.1016/j.apsb.2022.02.002. Epub 2022 Feb 11. PMID: 35865092; PMCID: PMC9293739.

2.        https://news.bms.com/news/details/2023/Bristol-Myers-Squibb-Strengthens-Neuroscience-Portfolio-with-Acquisition-of-Karuna-Therapeutics/default.aspx