Precision-Based Immuno-Molecular Augmentation (PBIMA)[1] and Personalized Edited Sequence (PES) is an approach to simultaneously activate or regulate the patient’s immune system as needed in a highly precise manner focusing it against a few specific antigens identified as disease cause.

PBIMA is a gene /protein /cell communication network-editing interface that finds and augments in repairing detected faults that globally effect an individual’s evolutionary regenerative adaptation and favors disease free survival.

NEO7 /Neo7Logix, offers this high affinity profiling, matching, selection based upon the patient’s own immune compatibility, immunoediting ability, and adaptation process in addition to treatment in the fight against disease. We are offering this platform technology to the market to collectively fight disease, save lives and give quality of life and longevity. This is a comprehensive solution from A to Z.

The Figures below illustrate process flow from patient sample through specified disease types:

_______[1] “PBIMA | Neo7Logix.” Neo7Logix  https://neo7logix.com/pbima 02/13/2020

The Human Immune System

The human immune system is the central focus in the defense and regulation against cancer, autoimmune, neurodegenerative and inflammatory driven diseases. Within the immuno-oncology arena checkpoint inhibitors have proven this work by exposing the tumor to the immune system and its ability to initiate tumor regression.

• In the case of autoimmunity, neurodegenerative and inflammatory driven disease networked protein to protein interactions and molecular biopathway interface.

• Collectively these pathway applications influenced regenerative adaptation against particular disease patterns an individual may encounter. In addition, focused considerations upon microbiome and microbe influences upon certain micro-editing characteristics of the immuno-molecular mechanisms in favorable evolutionary regenerative adaptation is crucial.

• Of late, there are varying degrees of success with patients responding remarkably and other patients weakly, due to the fact that profiling and selection process of high affinity patient neoantigen matches are not adequately and consistently performed. The lack of identifying compatible and high affinity antigens (Personalized Fragment Sequences) that will mark the cancer cells and tumor cells for destruction results in a higher incidence of failure. This results in more random selection of antigens riskier and can induce an unfavorable immune reaction with possible immune failure. The same can be said in cases of autoimmune, neurodegenerative and inflammatory driven diseases.

• Neoantigen innovations (new proteins expressed in cancer cells and tumor cells or expressed in molecular regulatory pathways), with a patient profiling for high affinity matching and selection within the cancer hallmark biological pathways and HLA compatibility schema, will yield higher specificity and induce immunoediting features that are favorable in cancer regression and less likely to provoke unfavorable autoimmune reactions. This will unlock the power of immune based therapies in larger number of patients, for longer periods of time and with greater efficacy and outcomes.

Fragment Sequence Editing Selection

(PBIMA)

There are complex questions within this neoantigen science that impede the ability to be a primary clinical reality. These are questions that NEO7 takes seriously. What is the best neoantigen to use in a given patient? What are the best ways to present neoantigens and connect them to an immune system primed for a fight? How best to mix and match neoantigen strategies with other existing immuno- oncology therapies? And, most importantly, what is the path forward for companies developing neoantigen-based innovations to make a real impact for patients? NEO7 is answering these questions. These essential questions and complexities are why Neo7Logix has developed the process called Precision-Based Immuno-Molecular Augmentation (PBIMA).

• PBIMA is a gene / protein / cell communication network editing interface that finds and augments in repairing detected faults that globally affect an individual’s evolutionary regenerative adaptation and favors disease free survival.

• NEO7 / Neo7Logix, offers this high affinity profiling, matching and selection based upon the patient’s own immune compatibility, immunoediting ability and adaptation process in addition to treatment in the fight against disease. We are offering this platform technology to the market to collectively fight disease, save lives and give quality of life and longevity. This is a comprehensive solution from A to Z.

Clinical Outcomes In Personalized Design

Over 500 patients have been treated with personalized immunopeptide sequence design safely and effectively with no serious adverse events. Studies have proven safety of use in humans as described in PBIMA Investigator’s Brochure.

PBIMA offers a remarkably high efficacy for the following disease states resulting from administration of personalized PBIMA design that otherwise had no effective treatment or given up by standard of care and considered incurable:

• Cancers: Multiple Myeloma, Melanoma, Breast Cancer, Colon Cancer, Lymphoma, Leukemia, Lymphoplasmacytic Lymphoma, Pancreatic Cancer, Lung Cancer, Bladder Cancer Thyroid Cancer and Brain Cancers.

• Autoimmune Disease Inflammation: MS, SLE, ALS, Scleroderma, Mixed Connective Tissue Disease, Hashimoto’s Thyroiditis, Rheumatoid Arthritis and Autoimmune Related Inflammation.

• Neurodegenerative Disease: Alzheimer’s Disease, Parkinson’s Disease, Dementia, Brain Inflammatory Disease, CNS Degenerative Inflammation.

Efficacy is clinically evaluated by commonly shared indicators including remission of disease, optimized quality of life, extended disease-free survival all resulting from personalized patient focus and not a single disease focus. Precision design offers more than diagnostic criteria and demonstrates highly specified molecular biological pathway / protein to protein faults that reveal clinical biomarkers and therapeutic candidate solutions for key causative factors in the individual’s disease presentation.

Current Drug Discovery Model

Conventional Pharmaceuticals:

• The development cycle for a single drug for a single disease is estimated at 12-15 years before being released to the market if not placed on hold or cut entirely after spending an estimated $3 billion dollars. The chance for a new drug to actually make it to market is thus only 1 in 5,000.  From 2012 to 2017, the Food and Drug Administration (FDA) issued 2,028 enforcement reports for drug product recall.  There were 195 drugs were pulled from the market for safety risk and serious adverse / damaging effects.

• A costly price tag for a drug that has one indication with limited efficacy and higher risk of serious adverse reactions with potential damaging end organ effects predisposing to other serious diseases.

• The aftermath is multi-hundreds of billions of dollars of revenue by an approved harmful drug pulled with damaging health effects experienced by the patients that physicians prescribed for over a period of years. A compounded dilemma that cripples our healthcare system and the patrons that depend upon it for solutions.

Personalized Therapeutics:

• The development cycle for personalized therapeutics designed uniquely to a person’s molecular profile is estimated at 7-12 weeks. There are no risks of serious adverse effects and / or complications in comparison to current drug models.

• Precision analytics unique to patients mapping and selecting matched therapeutic editing designs do not have a $3 billion dollar price tag for development with uncertainty to whether it can make it to market, work as designed or carry heavy risk of failure and harmful outcomes to patients. Revenue share for return on investment on a personalized therapeutic application is based upon global figures.

•  Commercialization of personalized therapeutic design is an economical design with potential of helping multi-billions of patients world-wide. The return on investment serves the patient well, physicians that are treating their patients, investors, public health and welfare by offering effective solutions in optimizing health and longevity and the regulatory agencies assuring safety for patients. Thereby, decreasing health disparities exponentially.

Revolutionizing Standard of Care

Personalized precision medicine demonstrates the potential of changing the standard of care as we know it. Allied Market Research valued the market at $3.5 trillion in 2016 and estimated it to reach $7.7 trillion by 2023, with a CAGR of 11.9% from 2017-2023. Such a high market value is a testament to the rapid advancement of this field, which hopes to provide customized treatment not only for curing ailments but also for preventing them in the future. Estimated growth actually surpasses the projected growth prediction estimated in 2015.

Immunotherapy Cost Comparison

CAR-T

• Cell therapy is a cutting-edge approach that begins with collecting a patient’s T cells through a process called leukapheresis. These T cells are then isolated and genetically engineered to make them more effective at targeting certain cancer cells.

• Chimeric antigen receptors (CARs) are defined as genetically engineered allogeneic cells that are developed in the laboratory and infused into a patient to help in detecting and fighting cancer cells. The protein constructs stimulate anti-cancer T-cells, which in turn boost a patient’s immune system.

• Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, followed by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or non-viral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.mRNA has increasingly growing concern and association with serious adverse effects and serious cytokine crisis inflammation.

• Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors.

• CAR-T immunotherapy is not completely personalized to the patient due to its allogeneic components which increase the risk of serious adverse events and toxic reactions. Cytokine related inflammation, neurotoxicity and other adverse disturbances as noted in clinical trials.

• CAR-T has a formidable price tag and has sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen. But the price tags — enormous as they are (nearly half a million [$475,000] for tisagenlecleucel [Kymriah, Novartis] and over a third of a million [$373,000] for axicabtagene ciloleucel [Yescarta, Kite Pharma]— cover only the cost of the drug itself. This doesn’t include other incurred health care costs associated with its use.

PBIMA

•  Conventional immunotherapy operates in the realm of “one size fits all,” which is the current landscape of conventional medicine. The primary flaw of this system is a failure of emphasis upon a uniqueness of the treatment design, more particularly, the customization of the treatment to “fit” the individual.

• Personalized immunotherapy is architected upon the unique molecular, biological and individual evolutionary adaptation design of the person.  An engineered customization that considers the intricacy and complexities of all the systems that keep an individual healthy and disease-free survival.

• “Best fit” optimization for an individual is in contrast to generalized random therapeutic distribution and selection, which places emphasis upon disease rather than centering upon the unique wholeness of the individual facilitating wellness and health longevity.

• PBIMA doesn’t use allogeneic elements, it strictly focuses on the immune compatibility and focability of the patient. PBIMA derived immunopeptides can be combined with cell therapy approaches to reengineer and program T cell responses with compatibility, affordably and with low risk of adverse reactions or toxicity because it is uniquely precisioned to the patient.

• PBIMA’s estimated cost of treatment in comparison to CAR-T is significantly less. PBIMA complete precision profiling including all required NGS, proteomics, precision analytics, synthesis and manufacturing currently is approximately $110K depending upon number of sequences in the patient design for four clinical rounds of treatment over an 18-month period spaced 8-12 weeks apart depending upon patient clinical progress.  This is for the PBIMA peptides and does not include clinical costs or other therapies incurred clinically.

With time, the cost will significantly reduce with in-house synthesis / development / final product fill-finish. Neo7Logix hopefully will cut development cost by at least 50% of the above price range listed offering the full four-cycle peptide treatment. Hopefully this will be sooner rather than later. Again, clinical costs are additional and variable dependent on the individual patient needs.

Question and Answer on Neo7Logix peptides

Why are the peptides from Neo7Logix so different from other clinics offering peptide therapies?

Neo7Logix is analyzing patient data from blood, urine, and tumor sample if for a cancer patient. From this data Neo7Logix will map (focus on an area) and rank (most important downward) the peptides that would be of greatest benefit to the patient. The other clinics are taking “off the shelf” peptides, usually from several dozen choices, to design what may help the patient. In comparison, Neo7Logix has literally over 4 billion choices (4,151,347,200) from which to personally design what is the most appropriate therapy for the specific individual.

This difference can be compared to going into a fast food restaurant and choosing something from off the menu of several dozen items. That food is not necessarily cooked specifically for each customer but is very general. In comparison, Neo7Logix’s peptides are built explicitly for each and every individual. Two patients might have the very same diagnosis, but the peptides are likely totally unique for each individual. Here in our restaurant example, Neo7Logix has an immensely broad menu of the very finest quality and each item is prepared specifically and exactly for desires of the person ordering with nothing being pre-prepared.