We are dedicated to developing highly selective medicines for patients. It is our goal to design and clinically develop patient friendly therapies with higher efficacy than the current standard of care. The more precise a therapeutic agent is designed for the individual needs of patients the better the potential outcome. We focus currently on two disease areas, infectious diseases and oncology, both have high mortality rates and inadequate treatment options.
Leukemia is a container term referrring to a diverse group of “blood” cancers with a distinctly different clinical behaviour that typically starts in the bone marrow where it impairs its normal role in forming a wide variety of normal blood cells.
In 2015, leukemia was present in over 2 million people worldwide (about 250,000 in the USA) and caused over 350,000 deaths globally. These numbers are rising steadily, especially in the Western World.
Development of novel drugs (often causing serious and long-lasting side-effects) and further improvements of existing treatment schemes have lead to steady prognostic improvement, but unfortunately some forms of leukemia are still characterized by very few therapeutic options and, consequently, poor survival rates.
Leukemic cells often contain chromosomal anomalies that are subtype-specific and have provided valuable clues for both diagnosis and treatment schemes. These recurrent chromosomal aberrations (often resulting in specific gene fusions) have also increasingly been used for target selection in the development of novel “magic bullet” approaches that specifically target the result of these genetic alterations.
Biomea has analyzed cytogenetic pointers recurrently associated with some forms of leukemia that are still characterized by limited therapeutic options. Unraveling the pathogenic signaling cascades that are fed by these fusion genes has allowed us to select novel targets and design drugs that specifically disrupt the leukemia-specific signals that drive the proliferation of these devastating cancers.
Based on excellent in-vitro activity of some of our first-generation leads, we are currently further optimizing the design of these novel scaffolds.
Small Molecule Development
At Biomea, we target key enzymes that are critical to the sustainability of the underlying disease. Using proprietary binding modalities and X-Ray crystal structures, novel scaffolds are designed to provide optimal protein engagement while maintaining drug-like properties.
With the novel scaffolds in hand, our in-house medicinal chemists design modern chemical synthesis schemes and further optimize the underlying architecture.
Infectious Diseases Program
Antibiotic resistance among clinically relevant bacterial species is a rapidly increasing, global problem. Currently, 700.000 people die from resistant infections every year, and it has been estimated that by 2050, 10 million lives and a cumulative 100 trillion US$ of economic output might be at risk annually due to the rise of drug-resistant infections.
At the same time, in recent decades, the discovery and development of new antibiotics have slowed dramatically as scientific barriers to drug discovery, regulatory challenges, and diminishing returns on investment have led major drug companies to scale back or abandon their antibiotic research.
Biomea Health seeks to fill this void of unmet clinical need by applying a proprietary, novel, and highly innovative approach to overcome some of the challenges that have traditionally limited the success of computational medicinal chemistry-based drug design efforts in the antibiotics space, and allow for the exploration of targets that were previously deemed hard or impossible to target or have consistently failed to deliver new drugs despite significant developmental efforts in the past. Our antibiotics development program currently focuses on the development of several new classes of antibiotics that target a wide variety of the Gram-negative bacteria that have been listed by the WHO and U.S.A. CDC as (multi drug-resistant) “superbugs” for which novel treatment options are desperately needed.
To this end, we have designed a series of new chemical scaffolds and a library of corresponding lead compounds that target various enzymes that are essential for active growth in Gram-negative bacteria.
Antibiotics Development Program
Structural impact analysis of naturally occurring structural variation at critical amino acid residues within one of our target proteins allows us to assess possible structural design constraints while developing novel chemical scaffolds with broad spectrum antibacterial activity.
By considering these variations at the earliest stages of our rational drug design process, we aim at designing NMEs that are broad spectrum by design.
We are applying computational chemistry methods to calculate binding efficiencies of our novel scaffolds on target protein variants found in clinically relevant Gram-negative bacteria, and use this information to drive our lead selection.
As shown in this table, for both the reference target protein as well as the main double amino acid variant, BMA-01, BMA-11, and BMA-13 outperform some of the benchmark molecules (ref. compounds 1 & 2*) in terms of binding score, whereas others show a disqualifying reduced tolerance towards target protein plasticity.
In addition, achieving binding scores that are close to, or even exceeding those of the natural substrate (in blue), significantly adds to the anticipated potency of our NMEs as it positively impacts PK by improving target competition.
* ref. compound 2 is a clinical stage compound