Fermenting pharmaceuticals to reduce adduct risks coupled with functional enzyme metrics

A method of reducing mutagen exposure risk associated with administration of a therapeutic agent, the method comprising:

• (a) fermenting ex vivo, outside the body, and prior to administration to a subject, the therapeutic agent either (i) in a mixture together with at least one adjunct component or (ii) separately from one or more adjunct components;
• (b) when the therapeutic agent is fermented according to step (a)(ii), either (α) combining the fermented therapeutic agent with one or more adjunct components that have been fermented ex vivo, outside the body, and prior to administration, to form a fermented composition, or (β) administering the fermented therapeutic agent and the one or more adjunct components that have been fermented ex vivo, outside the body, and prior to administration, at separate times relative to one another;
• (c) controlling, during fermentation of the therapeutic agent and/or the one or more adjunct components, at least one fermentation parameter selected from duration, temperature, pH, light exposure, wavelength, concentration, oxygen level, substrate availability, and order of addition;
• and (d) administering to the subject the mixture of step (a)(i), the fermented composition of step (b)(α), or the fermented therapeutic agent and the one or more adjunct components according to step (b)(β).

A method of adjusting a fermented therapeutic regimen for a subject, the method comprising:

• (a) administering to the subject a fermented composition comprising a therapeutic agent and one or more adjunct components, wherein the therapeutic agent was fermented ex vivo, outside the body, and prior to administration;
• (b) obtaining or receiving biomarker data for the subject, wherein the biomarker data comprises one or more mutagen-related adductomic endpoints;
• (c) obtaining or receiving one or more functional protein metrics for the subject;
• (d) comparing the biomarker data and the one or more functional protein metrics to comparator data comprising one or more baseline values and/or one or more threshold values;
• (e) determining, based on the comparing of step (d), whether a change in the one or more mutagen-related adductomic endpoints is corroborated by a corresponding change or trend in at least one of the one or more functional protein metrics;
• and (f) determining, based on steps (d) and (e), whether a subsequent administration should be adjusted or maintained and, when adjustment is indicated, modifying at least one of:
• (i) a selection of the one or more adjunct components, (ii) an amount of at least one adjunct component, (iii) an amount or selection of the therapeutic agent, (iv) timing of administration of at least one of the one or more adjunct components relative to administration of the therapeutic agent, or (v) one or more fermentation parameters.

A system for generating regimen instructions for a subject based on biomarker data, the system comprising:

• (a) an interface and/or communication module configured to receive biomarker data for the subject, wherein the biomarker data comprises one or more mutagen-related adductomic endpoint values and, in some embodiments, one or more functional protein metrics and/or one or more pharmacokinetic (PK) endpoint values and/or pharmacodynamic (PD) endpoint values;
• (b) a memory storing comparator data;
• (c) one or more controllers and/or processors configured to compare the biomarker data to the comparator data and, responsive to the comparing, determine an adjustment to a subsequent ex vivo fermentation of a mixture comprising a therapeutic agent and one or more adjunct components, wherein the therapeutic agent is fermented outside the body and prior to administration;
• and (d) an output configured to provide updated fermentation and/or preparation instructions specifying the adjustment, wherein the updated fermentation and/or preparation instructions specify at least one of:
• (i) a selection of the one or more adjunct components;
• (ii) an amount of at least one adjunct component;
• (iii) an amount of the therapeutic agent;
• (iv) one or more fermentation parameters selected from fermentation duration, temperature, pH, light exposure, wavelength, concentration, oxygen level, substrate availability, and order of addition;
• or (v) a timing of administration of the fermented mixture.

A system comprising:

• (a) an organizer comprising one or more removable modules configured to store one or more components of a fermentable mixture;
• (b) a vessel configured to ferment, outside the body and prior to administration, a composition comprising a therapeutic agent and one or more adjunct components;
• (c) one or more controllers configured to monitor and/or control at least one fermentation parameter selected from duration, temperature, pH, light exposure, wavelength, concentration, oxygen level, substrate availability, and order of addition;
• and (d) an interface and/or communication module configured to receive biomarker data for a subject, wherein the biomarker data comprises one or more adductomic endpoints and/or one or more functional protein metrics, and to output updated fermentation and/or preparation instructions based on the received biomarker data and/or clinical data.