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March 2019

2019 Market Report: Novel Technologies for Delivery of Proteins, Antibodies and Nucleic Acids, 2019-2030

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ICBII Interview Transcript-Chapter 12.3.2
and Globe Newswire, March 29, 2019

Ram Bhatt
CEO, Chairman and Founder ICB International

Roots Analysis: Can you tell us about ICB International?

ICB International, Inc: ICB International, (“ICBII”), was founded in 2008 with the aim of developing a novel technology to transport drugs across the blood brain barrier (BBB). The impermeability of the BBB has stymied progress for developing disease altering therapies for CNS disorders for centuries. The prevalence of Alzheimer’s and Parkinson’s diseases is high; more than 55 million individuals are globally suffering from these diseases. However, there are no diagnostics and curative therapeutics approved for these indications. Further, although the costs incurred in the R&D of diagnostics and therapeutics for these neurodegenerative disorders has been extremely high (USD Billions), there have not been any good outcomes. One of the primary reasons for the failure of recent clinical trials using amyloid-beta mouse monoclonal antibodies may well be due to the poor brain uptake of these drugs. Literature indicates that nearly 98% of all therapeutics do not reach the target site in the brain in required therapeutic concentrations.

Our company has developed technology to overcome the BBB challenge. After extensive research carried out over the last five to seven years, we were able to develop novel antibody mimics, referred to as SMART Molecules (SMs), that were shown to cross the BBB in mouse models of Alzheimer’s and Parkinson’s diseases. This research was validated by a third party based in San Diego. SMs (potential drugs) have not been only proven to cross the BBB but also bind to the specific disease targets in the brain of different animal models, and modulate the function of these targets. Post the successful completion of the proof-of-concept studies in transgenic animal models, the company intends to proceed with the clinical trials in human subjects.

Roots Analysis: In your opinion, what can be the other reasons for high rate of failure of the drugs designed to treat Alzheimer’s disease?

ICB International: Let us first make it clear that CNS diseases cannot be treated unless the disease altering drugs reach the brain in concentrations adequate for therapeutic effect. 0.1% brain uptake will not suffice. Another reason for the failure could be that amyloid β may not be the right target for treating Alzheimer’s disease, although I believe once the plaque is formed, it has to be reduced/cleared to alleviate its toxic effect. Also, Alzheimer’s is a very complex disorder. Without understanding the disease pathology, it will be difficult to design drugs that intervene in the disease progression.

Roots Analysis: Can you share some details on your Specific Molecular Architecture for Recognition and Therapy (SMART) Molecules platform? Is it in early stages of development?

ICB International: Classical monoclonal antibodies have a molecular weight ranging between 150-160 KDa, and are made up of two heavy and light chains. The molecules of our SMART technology do not have the light chains. As a result of this and some additional manipulations, our antibodies are very small with a molecular weight of only 46 KDa. This configuration enables the SMs to efficiently cross the BBB.
We are a clinical stage company. We have conducted most of the pre-clinical animal studies. Currently, we are developing manufacturing protocols that are in compliance with GMP protocols of the FDA.

Roots Analysis: Is SMART Molecules platform a drug delivery technology or a drug development technology?

ICB International: SMART platform is a drug development technology. However, it has the capability to transport any bio-therapeutic, such as an antibody, an enzyme, a DNA or a protein, to the brain. The technology is designed in a way that it enables the drug to target a particular errant protein in the brain; for instance, aggregated α-synuclein in case of Parkinson’s disease and tau tangles in Alzheimer’s disease. Also, any pharmaceutical agent can be attached to the SMART molecule and can be transported across the BBB into the CNS of animals. Thus, our technology is not only a delivery platform, but also a therapeutic platform

Roots Analysis: Is your technology available for licensing to other companies?

ICB International: Yes, we have on-going discussions with three international pharmaceutical companies. These companies are interested in employing our SMART Molecules technology for their products.

Roots Analysis: What is the route of administration for molecules based on SMART Platform?

ICB International: The molecules are administered through the intravenous route as the transport across the BBB through this route is proved to be very efficient. For instance, in case of classical mouse antibodies, the brain uptake of these molecules is about 0.1%; however, by the use of our technology, this value can be increased up to 15%. This has been validated in mice and I believe that the same can be achieved in humans as well.

Roots Analysis: What are the major advantages of the molecules derived from this technology?

ICB International: Efficient BBB permeability, long serum half-life, selective targeting of CNS targets, inexpensive scale-up, and adaptability to any new protein biomarker are some of the major advantages. Serum half-life of our SMs derived from this technology is eight days. SMs have the capability to reach the CNS in adequate concentrations to selectively bind to the biological targets, such as amyloid β and tau, and reduce their burden with very few, low dose tail vein injections in mice. In some experiments, we have seen brain uptake as high as 15% when compared brain to serum ratio. We have been able to conduct pre-clinical studies in mice with low (60 to 100 ug) intravenous doses of SMs. These studies revealed that our SMs are capable of reducing the burden of amyloid plaques or aggregated α-synuclein by almost 60% with 12 injections (one weekly injection for 12 weeks). In addition, our SMs technology allows detection and quantification of CNS errant protein by a simple intravenous injection of radiolabeled SM followed by a PET scan. We believe SMs have the potential for early detection and monitoring the effect of therapies on neurodegenerative diseases. Currently, there are no methods for a definite clinical diagnosis of Alzheimer’s or Parkinson’s diseases until after the post mortem. Our SMs technology will change that. To put it simply, SMs could potentially meet unmet medical need for diagnosis and disease altering therapies of CNS disorders such as Alzheimer’s disease, Parkinson’s disease, Progressive Supranuclear Palsy (PST), Multiple System Atrophy (MSA), glioblastoma, and many other neurological or storage disease disorders.

I would also like to mention that the Alzheimer’s transgenic mouse model used in our study has very aggressive disease pathology with an average life span of 8-10 months. However, in our study, we found that the treated mice survived for more than a year, 14-15 months. We are now very eager to test the effect of our SMs on patients.