Disclaimer: PBIMA-PES™ is a proprietary personalized vaccine of Neo7Logix and distributed under clinical research materials for patients’ use. PBIMA is currently not an FDA approved and commercially available product but is under investigational development for safety and efficacy. PBIMA is in the process of FDA submission and approval. Neo7Logix has obtained IRB approval for PBIMA use in patients by ANRI/NORI IRB #822019 in Arizona, USA. PBIMA quality is guaranteed by approved cGMP manufacturers. Physicians, practitioners, and institutions are administering PBIMA under informed consent, consistent with their standards of care in clinical practice and at their own risk.
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About The Product
PBIMA-PES™ is a personalized peptide therapy to be used in the treatment of cancer, autoimmune conditions, and inflammation-driven and neurodegenerative disease that has returned or has not responded to treatment. Precision targeted peptides can create an appropriate immune system response that is a potent therapy for disease. The precise combination, individualized for each patient, is designed to activate the immune system against neoantigens and self-antigens or to suppress autoimmune reaction against autoantigens. PBIMA-PES™ is a set of personalized edited sequences ranked and mapped by precision analytics. These sequences are administered to a patient in four 21-day cycles, spanning a 12- to 18-month period.
Specific Indications
PBIMA-PES™ is a promising experimental personalized treatment that is developed using the cutting-edge genomics technologies by in-depth analysis of the patient genome. It can be applied for the following diseases but not limited to:
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Cancers – Breast, bladder, lung, thyroid, brain, bone, colon, pancreatic, prostate, multiple myeloma, melanoma, lymphoma, lymphoplasmacytic lymphoma, leukemia, etc.
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Autoimmune Disease Inflammation – Multiple sclerosis (MS), systemic lupus erythematosus (SLE), scleroderma, mixed connective tissue disease, Hashimoto’s thyroiditis, rheumatoid arthritis, etc.
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Neurodegenerative Disease – Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), dementia, brain inflammatory diseases, CNS degeneration, etc.
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Useful For
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Cancer patients in non-remission, post chemotherapy, and post-surgical excision of tumor.
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Patients with advanced disease unsuitable for chemotherapy or standard therapy.
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Regulation of the autoimmune system and inflammatory diseases.
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Neurodegenerative diseases for which pharmaceutical approaches have very limited ability.
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Quality of life improvement.
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Anti-aging for those wanting a more robust immune system to deter diseases of old age.
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Key Properties
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Creates a very strong immune response/function to recognize disease cytokines in immunocompromised patients.
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Gives high potency and efficacy to activate, defend, and regulate the immune system to provide for disease-free survival.
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Pharmacology
PBIMA-PES™ provides a high specificity to T cells for initiating the patient’s immune defense, regulation, and adaptation. It reprograms the immune system for neutralizing and/or eradicating mutated cells in any stage of a disease process which includes prophylaxis, primary, and secondary stages.
PBIMA-PES™ consists of immune sequences for T cell activation aimed at correcting faults, and initiating or regulating pathways as revealed by patient’s own data. The neoantigens and selfantigens of PBIMA-PES™ modulate T cells in patients with cancer, autoimmune, and/or neurodegenerative disease.
Molecular Targets
Cancer and autoimmune diseases are first and foremost a failure of the immune system. PBIMAPES™ uses immunoediting to achieve an immune system “reset.” Immunoediting is a primary pushbutton feature required for initiating immune defenses.
With cancer, the tumor microenvironment is a “mixed bit” moiety, which includes elements of the immune system that are still working correctly. Yet, the tumor microenvironment is creating its own immunity to avoid immunosurveillance from outside its own environment. The intrinsic mechanisms of tumor defense and regression are based upon the elimination, equilibrium, and escape model. The three components are represented respectively as anti-tumor defense (tumor immunity), tumor dormancy, and tumor progression (Mittal et al., 2014).
Pharmacokinetics
PBIMA-PES™ contains personalized, matched neoantigens and self-antigens. There are no reports of serious adverse events in humans. The product is non-toxic; the design has not been shown to initiate an ADE (adverse drug event) risk in patient. The product poses minimal risk of biological contamination. It does not produce an unwanted immune response as it has only de novo amino acids.
Pharmacokinetic actions of personalized peptides are best seen by injection subcutaneous, intramuscular, intranodal, intratumoral, and intranasal. Oral administration is not an optimal delivery route.
Ref. Mittal, D., Gubin, M. M., Schreiber, R. D., & Smyth, M. J. (2014). New insights into cancer immunoediting and its three component phases– elimination, equilibrium and escape. Current opinion in immunology, 27, 16–25.
Clinical Data
The first generation (G1-PES) of PBIMA-PES™ was administered to more than 500 patients. Most had end-stage metastatic cancer and had failed standard of care. Other patients presented with autoimmune and neurodegenerative disorders. All these patients were put on the G1-PES 12- to 18-month therapy. Cancer patients demonstrated 58% clinical efficacy with 70% of the patients experiencing tumor regression and extended life survival of 3, 5, or 10 years. Their quality of life was between 8-10 in all cases while in treatment. Autoimmune patients demonstrated 90% recovery with extended remission and no recurrence of the disease. Neurodegenerative patients demonstrated slowed acceleration of disease with improvement in cognitive function, motor function, increased quality of life, and life extension.
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Typical reactions included a slight fever, flu-like symptoms for 1-2 days, and rash at route of administration site that lasted 2-3 days. All reactions were minor and self-limiting. All patients were free of SAEs (serious adverse effects) while receiving therapy.
Clinical Benefits
Recent clinical studies on personalized neoantigen therapy demonstrate that it is an effective anticancer treatment that helps to improve vitality and quality of life of cancer patients who have failed on conventional therapy of chemotherapy, surgery, and radiotherapy. The data shows complete tumor regression, with progression-free survival of patients (Ott et al., 2017; Chen et al., 2019).
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Personalized neoantigen therapy showed a low incidence of SAEs in 500 advanced cancer patients, including 174 prostate, 74 colon, 51 pancreatic and 43 gastric cancer patients (Yoshida K. et al., 2011). Moreover, favorable immune effects were observed which included disease stability. However, physicians should be on guard for rare SAEs associated with augmented immune responses.
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In our experience, PBIMA-PES™ provides patients with a substantially better QOL while they are addressing their disease process. Incoming patients reported their QOL was around 3 while engaged in prior treatments. Then with use of PBIMA-PES™, patients report an increase in QOL of 8 to 10, and we see that the therapy outcomes demonstrate a high level of success compared to standard of care.
Ref. Chen F., Wei J. and Liu B. (2019). Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest, 129(5):2056-2070.
Ott P. A., Hu Z., Keskin D. B., Shukla S. A., Sun J., Bozym D. J., Zhang W., Luoma A., Giobbie-Hurder A., Peter L., Chen C., Olive O., Carter T. A., Li S., Lieb D. J., Eisenhaure T., Gjini E., Stevens J., Lane W. J., Javeri, I. and Wu, C. J. (2017). An immunogenic personal neoantigen vaccine for patients with melanoma. Nature, 547(7662), 217–221.
Yoshida K, Noguchi M, Mine T, Komatsu N., Yutani S., Ueno T., Yanagimoto H., Kawano K., Itoh K., and Yamada A. (2011). Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases. Oncol Rep, 25(1):57-62.
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Ingredients
Precision personalized peptides are synthesized for each patient using pharmacological, cGMP certified de novo amino acids. Selected adjuvants are added.
PBIMA-PES™ is free of wheat, gluten, corn, soy, lactose, starch, sugars, yeast, genetically modified ingredients, mercury, and aluminum.
Dosage
The recommended maximum dose of PBIMA-PES™ is 0.76 mg/2 ml injection/dose/day which is 0.5 ml subcutaneous + 1.5 ml intramuscular once daily each cycle.
Depending upon the patient, it is possible the clinician may want to alter the proposed IND protocol initially and ramp up within 3-4 days to the full dose. In that case, an introductory test dose of 0.25 ml pooled peptide will be applied first to determine patient tolerance. After the test dose, subsequent dosing will be raised by 0.25 – 0.5 ml until the maximum dose (0.76 mg/2 ml/dose/day) is achieved.
Titrated dosing can be performed over a three-day period to observe tolerance and potential reactivity. When the maximum dose is reached, administration of the maximum dose will continue for 18 consecutive days thereafter.
PBIMA-PES™ administration is a 21-day cycle.
The total time of PBIMA-PES™ administration is for 4 cycles over a 12- to 18-month period. Cycles 1-2 should be 6-8 weeks apart and cycles 3-4 should be 12 weeks apart.
Cycles 3-4 may be extended to 21-30 days over an 18-month treatment window. The treatment window and cycling may be adjusted depending upon the patient’s response to the therapy; improvement in clinical signs, symptoms, improved quality of life based upon screening; and follow up diagnostic serology, pathology and imaging; as well as evidence of regression of cancer, tumor, proliferation, metastasis, and overall cancer burden.
Contraindications
The one contraindication is any type of immunosuppressant drugs including corticoid steroids, biologics, and organ transplant drugs.
Peptide therapy is contraindicated for pregnant and nursing females. However, these patients can take PBIMA-PES™ based on their physician’s judgment of their condition, and if they will give their physician a signed informed consent, acknowledging the potential risk.
Storage
Neo7Logix’s vials must be stored immediately at -20°C. The material may remain in such storage up to 12 months. After reconstitution, the vial must be used within a month. Keep the prepared vial refrigerated while being used during the 21-day cycle. For long-term storage (more than 12 months), PBIMA-PES™ should be stored at -80°C with desiccant in sealed containers to minimize content degradation. Under these conditions, the material can be stored for up to several years. This type of storage prevents degradation, oxidation, and the formation of secondary structures.
Use
The Neo7Logix pack contains 16 mg of PBIMA-PES™ as lyophilized powder in each of 4 amber glass vials, and 42 ml of PES-SOL™ solution for reconstitution in each of the other 4 vials. A 5 ml glass injector is also included; it can be reused upon sterilization.
When ready to use, remove 1 vial of PBMIA-PES™ (peptides) and 1 vial of PES-SOL. Keep the remainder of the Neo7Logix frozen for future use.
Prior to opening an individual PBIMA-PES™ vial and an individual PES-SOL™ vial, they should be brought to room temperature in a desiccator. Failure to warm the material beforehand can cause condensation to form on the product when the vial is opened (product tends to be hygroscopic). This will reduce the stability of the peptides.
Before reconstitution with PES-SOL™ solution, centrifuge the PBIMA-PES™ peptide vial at 12,000 x g for 20 seconds. This will help pellet the material for reconstitution.
Reconstitute 16 mg PBIMA-PES™ with 42 ml PES-SOL™ solution in a sterile space. After reconstitution, shake the vial gently 10 times and then administer 2 ml of the reconstituted solution (0.8mg/dose/day) to the patient once daily as 0.5 ml subcutaneous and 1.5 ml intramuscular. Refrigerate unused portion of vial.
Monitor the patient’s disease condition and administer for 21 days each cycle. Continue administration for 4 cycles 6-12 weeks apart over a 12-18 month period.