biorchestra

why rna-based
TERAPEUTICS?

Proteins are crucial molecules in our cells and are required by
all living organisms. The interaction between microRNA and
messenger RNA (mRNA) produces a transient set of
information cells use to express a protein from
information coded in the DNA.

Protein drugs made by recombinant protein technology
generate more than $200 billion in annual sales worldwide.
However, many proteins are present in cells, 1) including
enzymes related to epigenetics, 2) proteins expressed by
mitochondrial DNA, and 3) other important intracellular
proteins, which are considered inaccessible targets
by recombinant protein technology. If we develop RNA
drugs that can precisely regulate the expression of
these proteins using cytoplasmic gene expression systems
inside the body, we can make a bigger therapeutic impact
than the protein drugs currently on the market.

Several advantages can be obtained by directly
using the cytoplasmic gene expression systems
inside the body. Proteins expressed and regulated
inside the body can more strongly mimic original
proteins than proteins produced in vitro.
This induces minimal immunogenicity.

The production of proteins in vitro is
time-consuming and process-intensive and the proteins
may be unstable depending on the type of protein produced.
Furthermore, implementing a strategy for producing or
regulating multiple proteins will face even more
technical limitations. To address these unmet needs,
we are developing RNA sequences and RNA delivery
technology that deliver mRNA or microRNA
regulators effectively and safely.

Delivering modified mRNAs into the cytoplasm
can mimic proteins that function as epigenetic
enzymes, viral antigens and antibodies.
The delivered microRNA regulators can control
multiple protein functions impaired in diseases,
such as neurodegenerative diseases. Moreover,
unlike DNA-targeting therapeutics like gene therapy, 
which may insert DNA into the chromosome permanently,
the effects of RNA-based therapeutics can be temporary,
thus reducing the risk of irreversible cellular DNA
changes that may induce tumorigenesis.

OUR mRNA DRUG PLATFORM TECHHNOLOGIES

BIORCHESTRA Multiple mRNA regulation Drug = BMD

BMD is a therapeutic agent that regulates multiple mRNAs.

In order to effectively treat neurodegenerative diseases with complex pathogenesis, our logic is that it would be an effective approach
direction to regulate multiple mRNAs.

As various drugs targeting neurodegenerative diseases usually target one, they have low success rates and even if they succeed in
development, it is difficult to expect effective therapeutic effect.
Therefore, new drugs will still continue to be developed for a wide range of therapeutic effects.

With our BMD technology, we are developing therapeutics that effectively treats CNS diseases such as AD, PD, and ALS.

BIORCHESTRA Single mRNA regulation Drug = BSD

BSD is a therapeutic agent that contains a sequence that can effectively express a single mRNA in a cell.

The sequence that can effectively express a single mRNA in a cell can activate the human immune system by expressing sequences of
antigenic part in virus or bacteria.

In addition, the immune system corresponding to the cancer gene can be induced by analyzing information about cancer patients.

We have a unique Bioinformatics technology capable of analyzing bioinformation, through which we are building Neo-antigen program.

In-house RNA delivery System Development

Another strength of ours is that we have a production system in-house for RNA delivery vehicles.

We can produce drug products through our RNA delivery vehicle production system and plan to accelerate the pipeline expansion by setting up manufacturing facilities of GMP level in the near future. The advantage of the RNA delivery system in-house is that it can minimize RNA
drug development time.

This is because every time you develop an RNA drug, you need to optimize the RNA length and you can reduce the time to optimize the
polyion micelle structure to match the RNA length each time. This process is very important because it increases in vivo circulation
of micelles containing RNA and the rate of delivery to the target.

The fact that this process is possible in house means that we have the ability to quickly and accurately produce Well Quality controlled
materials.

Neurodegenerative diseases can make you unable to recognize
your loved one and lose important memories
and make it impossible to move freely

There are two major types of cells in the human brain. One is neurons which are responsible for cognitive abilities and the other is glial cell which cleans the surroundings of neurons and support their structure. The neurodegenerative proteinpathies (Figure 1), which should be self-degraded, are caused by dysfunction of both cells, depending on aging and genetic or environmental factors, and accumulate inside and outside of the cells, leading to cytotoxicity and eventually cell death. In the current technology, new drugs are being developed that have a mechanism to remove toxic substances accumulated outside the cell using biopharmaceutical called ‘Antibody’, rather than restoring the intracellular functions (Figure 2).

Figure 1. Disease-causing the neurodegenerative proteinpathies in brain.

Drugs on the current market are also medicines that inhibit the enzyme Acetylcholinesterase, which catalyzes the breakdown of a neurotransmitter (Acetylcholine) delivered signals between cells. It is obviously clear that antibodies for targeting toxic substances under development, and drugs on the market are also excellent drugs (Figure 2).However, We are moving one step further to develop drug to treat diseases. Ultimately, since the accumulation of these toxic substances is caused by intracellular dysfunction, we have developed a new biopharmaceutical to treat the inside of the cell. As the conditions of aging and disease progresses, cells also get sick and unable to respond on various stimuli because of lack of expression or loss of function in the proteins that maintain health, and eventually the cells die. Brain immune cells in normal people scavenge and degrade different types of toxins and regulate inflammatory responses. The neuronal cells in normal people block the production of toxic substances well and maintain the pathway, which transmit a signal through neurotransmitters. Therefore, our brain is free of toxic substances and we can think very well. We are demonstrating a mechanism for restoring sick cells to conditions like normal brain cells. The function of the cells is to return to normal brain that was healthy (Figure 3).
This is a powerful effect that can be applied to many neurodegenerative diseases, such as Lou Gehrig’s disease.

Figure 2. Type of drugs to treat existing Alzheimer’s disease.

This has the potential to have a fundamental therapeutic effect that is completely different in concept from the relief of symptom of drugs that are either FDA-approved or under development. Recently, the drug has also been shown to improve neuromuscular function in Lou Gehrig’s disease. We believe that it can be an innovative new drug for aging-related diseases such as neurodegenerative disease and neuromuscular disease.

Figure 3. Therapeutic effects of BMD-001 in Alzheimer’s disease brain.