ADiTxT

OVERVIEW
TECHNOLOGY
ADVANTAGES
DIFFERENTIATORS
Team

The discovery of immunosuppressive (anti-rejection) drugs has made possible life-saving organ transplantation procedures. While these drugs prevent or delay organ rejection, transplanted organs often ultimately fail, and about 40% survive for no more than 5 years1. Furthermore, immune suppression leads to significant undesirable side effects such as increased susceptibility to life-threatening infections and cancers because it is not specifically targeted towards the transplanted organs; rather, it indiscriminately and broadly suppresses immune function throughout the body.

We have an exclusive worldwide license for commercializing a nucleic acid-based technology named Apoptotic DNA Immunotherapy (ADi) which utilizes a novel approach that mimics the way our bodies naturally induce tolerance to our own tissues. While immune suppression requires continuous administration to prevent rejection of a transplanted organ, induction of tolerance has the potential to retrain the immune system to accept the organ for longer periods of time. Thus, ADi may allow patients to live with transplanted organs with significantly reduced dependence on immune suppression.ADi is a technology platform which we believe can be engineered to address a wide variety of indications. We are initially focusing on skin allotransplantation, a setting in which ADi treatment has demonstrated significantly improved survival of transplanted skin grafts in animal models.

A NEW APPROACH

The discovery of immunosuppressants (anti-rejection drugs), such as cyclosporine, has allowed survival of transplanted organs by preventing acute or early rejection. However, immunosuppressants fail to prevent the chronic or long-term rejection that occurs years after the initial transplant. About 40% of transplanted organs survive for no more than 5 years1. Furthermore, immune suppression leads to significant undesirable side effects such as increased susceptibility to life-threatening infections and cancers because it is not specifically targeted towards the transplanted organs; rather, it indiscriminately and broadly suppresses immune function throughout the body.

New, focused therapeutic approaches are needed that modulate only the small portion of immune cells that are involved in rejection of the transplanted organ, as this will be safer for patients than indiscriminate immune suppression. These approaches are referred to as immune tolerance. Therapeutically induced immune tolerance may not only be safer for patients, they could also potentially allow long-term survival of transplanted tissues and organs.

In the late 1990s, academic research was being conducted at the Transplant Center in Loma Linda University (LLU), for a project that secured initial funding through grants from the Department of Defense (DOD), which was funding projects with high probabilities of commercialization and potential benefit to the DOD. The direct benefit in this case was for skin grafting for burn victims. Twenty years of research at LLU and an affiliated incubator led to a series of discoveries that have been translated into a large patent portfolio that may be applied to the modulation of the immune system to induce tolerance to self and transplanted organs – tolerogenic immunotherapy.

We have an exclusive worldwide license for commercializing this nucleic acid-based technology called Apoptotic DNA Immunotherapy (ADi) which utilizes a novel approach that mimics the way our bodies naturally induce tolerance to our own tissues.

While immune suppression requires continuous administration to prevent acute or early rejection of transplanted organs, induction of tolerance has the potential to retrain the immune system to accept the organ for longer periods of time. Thus, ADi may allow patients to live with transplanted organs with significantly reduced dependence on immune suppression.

ADI TECHNOLOGY

ADi utilizes a novel approach that mimics the way our bodies naturally induce tolerance to our own tissues. It is a technology platform which we believe can be engineered to address a wide variety of indications.

ADi includes two DNA molecules which are designed to deliver signals to induce tolerance. The first DNA molecule encodes a pro-apoptotic protein, which induces ‘programmed’ cell death. This is a core component of the technology because it is intended to greatly increase the recruitment of dendritic cells which are implicated in regulating the immune system. The second DNA molecule encodes the protein of interest (guiding antigen), which is modified to promote a path of tolerance. The guiding antigen is intended to result in tolerance induction specific to the tissue where the protein is found.

ADi has been successfully tested in several preclinical models and its efficacy can be attributed to multiple factors:

ADi does not rely on a single mechanistic approach. It has multiple components that affect different arms of the immune system – antigen-specific, apoptotic, plasmid DNA which can be manipulated.
ADi activates key immune cells known to maintain tolerance in test animals and humans.
ADi has been successfully applied to a stringent transplantation model.
ADi is designed to be safely and can be repeatedly administered to achieve its full potential therapeutic effect, thereby increasing its potency.

Results shown are 5 weeks post-transplantation

	Allograft has been completely lost, only the scab remains
	Allograft not only survived, it remained fully functional with intact hair follicles from the white donor mouse

ADI ADVANTAGES

ADi is a nucleic acid-based technology ( e.g. , plasmid DNA-based) which we believe selectively suppresses only those immune cells involved in the rejection of tissue and organ transplants. It does so by tapping into the body’s natural process of cell death (apoptosis) to reprogram the immune system to stop unwanted attacks on self or transplanted tissues. In short, it retrains the immune system to become accepting of the organ much like how natural apoptosis reminds our immune system to be tolerant to our own “self” tissues. Thus, ADi may allow patients to live with transplanted organs with significantly reduced dependence on immune suppression.

While efforts have been made by various groups to promote tolerance through cell therapies and ex vivo manipulation of patient cells (takes place outside the body typically requiring hospitalization), to our knowledge, we will be unique in our approach of using in-body induction of apoptosis to promote tolerance to specific tissues. In addition, ADi treatment itself does not require hospitalization, only an injection in minute amounts directly into the skin.

Reduce Chronic Rejection

While immunosuppressants control acute rejection during the early time-period after receiving an organ, chronic rejection of the organ that occurs one or more years after the transplant procedure continues to pose a major challenge for organ recipients.

Chronic rejection has been likened to autoimmunity (a misdirected immune response that occurs when the immune system goes awry), where specific tissues in the transplanted organ are attacked by the immune system. In other words, chronic rejection may not be caused just by differences between the donor and the recipient, but rather by an immune response by the recipient to specific tissues in the organ. With ADi’s ability to tolerize to specific tissues in a transplanted organ, it has the potential to reduce incidences of chronic rejection.

Moreover, preclinical studies have demonstrated that ADi treatment significantly and substantially prolongs graft survival, in addition to successfully “reversing” other established immune-mediated inflammatory processes.

Reduce Immune Suppression

Studies in animal models have shown that conditioning/desensitizing the animals to receive the transplant, prolongs the survival of the transplanted tissue or organ. These studies have used repeated exposure to low doses of protein components in specific organs to reduce immunologic recognition and attack on the transplanted organ.

Based on some of our data, we believe that with ADi treatment, recipients can be conditioned/desensitized ahead of transplantation, thereby retraining the immune system to more readily accept the organ and also reduce the levels of immunosuppressive drugs needed post-transplantation.

Hypersensitivity

Studies have shown that hypersensitivity increases the rate of organ rejection. Hypersensitivity can occur in previously-transplanted patients, patients who have given birth, and patients who have previously received blood transfusions. With more than 116,000 patients on transplant waiting lists in the U.S. alone, hypersensitive patients have much lower chances at qualifying to receive organs due to their increased risk of rejection – even with immune suppression.

Sadly, transplanted patients have a probability of needing re-transplantation at some point due to eventual chronic rejection of their transplanted organ, with the possible exception of some newborn recipients. With increased incidence of hypersensitivity, these patients may never have the opportunity to receive another organ. Based on experimental data, we believe that ADi may have the potential to address this hypersensitivity issue providing these individuals better opportunities at receiving an organ transplantation.

ADi Key Differentiators

EASE OF DELIVERY

Therapeutic products are typically administered systemically (i.e., by mouth in pill form or injected intramuscularly/intravenously). This requires repeated large doses of the drug to allow sufficient concentrations to reach the affected sites. ADi is a DNA-based product that can be injected directly into the skin where the target cells of the immune system reside, thereby significantly simplifying the delivery of the product and reducing the amount of product needed.

BETTER SAFETY PROFILE

DNA-based products are generally considered safe. In fact, over the last twenty years, several DNA-based vaccines have been evaluated in clinical trials for cancer and infectious diseases and no severe adverse events have been reported. In addition, DNA-based products generally do not result in allergic responses, which lend themselves to repeat dosing as may be required by ADi based therapeutics.

COST OF GOODS ADVANTAGE

ADi products are DNA-based and easy to manufacture at a low cost. Furthermore, DNA-based products are very stable and do not require adherence to cold chain (temperature-controlled) protocols for shipping. This also makes the product ideal for global distribution.

SIMPLIFIED THERAPY DELIVERY SYSTEM

We believe that tolerance induction using ADi may potentially not require hospitalization because it can be simply injected into the skin. This approach reduces treatment costs and complexities in treatment delivery. The anticipated administration of ADi will include an initial priming regimen that will require injections administered once a week for several weeks. Thereafter, booster or maintenance doses will be potentially be provided on an individual basis as determined by immune and inflammation testing. ADi treatments will be significantly more convenient and comfortable for patients because they do not require removal of patient cells for ex vivo manipulation.

Our team of scientific experts and innovation commercialization entrepreneurs come from a variety of fields and backgrounds, with a collective experience that range from founding startup biotech companies, to developing and marketing biopharmaceutical products, to designing clinical trials, and management of private and public companies.

Meet Our Team

Leonard L. Bailey, MD
Co-Founder and Chairman

Dr. Bailey is an internationally recognized authority on congenital heart surgery and infant heart transplantation. His pioneering work in infant heart transplantation has enabled babies born with otherwise fatal heart deformities to be given a second chance at life and resulted in babies being added to the national organ transplant registry. He performed the first successful human-to-human heart transplantation in a newborn baby and has performed countless lifesaving procedures at Loma Linda University Children’s Hospital, where he served as Surgeon-in-Chief. Dr. Bailey retired from LLU in 2018 where he served as a distinguished professor of transplantation surgery and was part of the team that developed ADi.

Amro Albanna
Co-founder and Chief Executive Officer

Founded multiple technology startups in various sectors including software, hardware, and medical devices. Led private and public financing and positioned companies for mergers and acquisitions.

Shahrokh Shabahang, DDS, MS, PhD
Co-founder and Chief Technology Officer

Founded multiple biotech startups with experience in commercializing new life science technologies. Inventor of seven issued patents in life sciences. Expert in immunology and immune tolerance.

David Briones
Interim CFO

Managed the public company and hedge fund at Bartolomei Pucciarelli (LLC). Former auditor with PricewaterhouseCoopers LLP who specialized in the financial services group, and most notably worked the MONY Group, Prudential Financial, and MetLife initial public offerings.

Waldo Concepcion
MD Clinical Advisor

Pediatric and adult liver and kidney transplant surgeon for 31 years. Co-developed Liver Transplant Program at California Pacific Medical Center, founded Pediatric Liver Program at Loma Linda University, and served as Director over the Multi-Organ Transplant Program.

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