Does a longitudinal state trajectory capture clinically meaningful change in PTSD?
NeXus NeuroInformatics, Inc. (operating clinical company; parent brand: Nexus Concordat, Inc.) applies to the September 2026 Waypoints cycle under invitation from David Kim, Business Analyst, Berg Innovation Exchange. AetherProtocols — our deterministic longitudinal state-computation architecture — already exists. What we are asking Mayo to build with us is a clinical evaluation relationship around a single restrained scientific claim.
This is a clinical-evaluation question, not an engineering question and not a training question. The state trajectory is produced by an architecture we already own and can already run. The open question is whether it corresponds to clinical change in real people, over real time, in a bounded first-use context: adult veterans and active-duty service members with established PTSD. Our submitted federal research programs are designed to test the mathematics at the implementation and population level. Mayo is the piece that can test the mathematics at the level of the individual person over time — the level at which clinical decisions are actually made.
Canonical stack
Six actors, kept operationally separate for regulatory clarity. Each has one role; conflating them dissolves the evidence chain.
| Layer / Partner | Role |
|---|---|
| AetherAnalyte | Acquisition and qualification of observations. Armband hardware plus per-observation tagging of timing, calibration, quality, uncertainty, and provenance. This is the input side: the observations, tagged with everything needed to trust them. |
| AetherProtocols | Deterministic longitudinal state-computation architecture operating inside the NLM. Given qualified observations, computes individualized, uncertainty-bearing state trajectories. |
| NLM (Neurochemical Language Model) | Downstream learned interpretation of the state trajectory. Language emission, clinical framing, HCP-facing communication. Learned, not deterministic. |
| Scyla | Execution and compiler layer. Runs the stack. Implementation conformance is demonstrated independently of the stack it executes. |
| Track-1 analytical / assay-validation partner (under NDA; not named at this stage) | Analytical / assay validation of the biomarker measurements themselves. Executed mutual NDA in force. |
| Mayo Clinic (Track 2 partner — this application) | Clinical study design, longitudinal data access, PTSD expertise, endpoint interpretation, prospective validation. |
The two tracks are complementary and non-overlapping. Track 1 addresses whether the biomarker measurements themselves hold up analytically. Mayo (Track 2) addresses whether the state trajectories those measurements describe correspond to real clinical change.
State behavior — what the deterministic layer guarantees
- State persists. A previously computed trajectory carries into the current computation. A person is not re-initialized every session.
- State decays. Pharmacokinetic-style decay across observation gaps. Decay constants are architectural, not learned.
- Missing observations are not zero. Absence of a measurement is not evidence of a low value. Uncertainty widens when data is missing.
- Missing observations are not recovery. Absence of a stress signal is not evidence the person is well. The state model does not silently improve when it stops seeing bad news.
- Response is state-, history-, context-, and sensitivity-dependent. The output depends on the current state, the accumulated trajectory, the operational context, and the individualized sensitivity parameters — not on the last observation alone.
Where the surrounding federal programs stop — and where Mayo begins
Our federal research proposals are designed around three complementary validation axes. Each addresses a different validation question. None of them, by design, answers the individual-level question.
| Program | What it tests | What it cannot test |
|---|---|---|
| FDA U01 GRANT14747560 submitted 2026-08-20; in Pre-Award Risk Assessment |
Implementation fidelity (does the computation faithfully execute the specification?) and cohort-level correspondence between the state trajectory and a standardized reference biomarker panel drawn at prespecified sampling points in an adult combat-veteran PTSD observational cohort. | Whether the trajectory is correct for an individual person over time. Reference biomarker panels validate the mathematics against population-averaged biology, not against dense within-person biology. |
| NIH Transformative R01 GRANT14753616 submitted 2026-09-03 (RFA-RM-27-003) |
Counterfactual falsification infrastructure — whether the measurement approach behaves correctly across controlled histories starting from the same parameterized profile. Explicitly not derived from any living individual; public dataset use at the population level only. | Whether the trajectory tracks a real individual's real state dynamics day by day. The R01, by architectural discipline, is not entity-grounded. |
| Track-1 partner (under NDA) | Analytical / assay validation of the biomarker measurements themselves. | Anything above the measurement layer. |
What the three programs above cannot, by design, answer is the individual-scale question: for a specific person, over their specific history of medication, stressors, sleep, and clinical events, does the AetherProtocols state trajectory correctly track what actually happened in that person? Clinical decisions are made at that level. Regulatory endpoints ultimately have to defend claims at that level. This is the validation gap Mayo is uniquely positioned to help close.
What we are asking Mayo to bring
- Clinical study design. Faculty co-authorship of the prospective-evaluation protocol that tests whether AetherProtocols state trajectories correspond to clinically meaningful change in adults with established PTSD over time. Endpoint hierarchy, cadence, comparators, blinding, uncertainty-handling, stopping rules.
- Longitudinal data access. Clinically characterized human data with the variables, cadence, consent, and time-alignment the evaluation requires. Specific dataset scoping is a design output, not a design input; we are not naming a target asset here because doing so would put the cart before the study protocol.
- Psychiatry and PTSD expertise. Faculty familiarity with combat-trauma and non-combat adult PTSD presentation, CAPS-5 administration, and the clinical-state transitions the evaluation is designed to detect. Curation of the three canonical archetypes exercised on the synthetic testbench (below).
- Biomarker and digital-endpoint interpretation. Mayo's perspective on what a clinically meaningful state-trajectory change looks like in the CAPS-5 arousal-and-reactivity subscale, and how the NeXus AI ART instrument's hierarchically-ordered secondary-endpoint framing should be tuned against the evaluation record.
- Prospective validation. The evaluation itself — a jointly designed prospective study in adult-PTSD populations run with an appropriate Mayo clinical research team, subject to agreement, IRB review, data permissions, and funding, that closes the loop from state trajectory to clinical change and produces the record the downstream CDER COA Qualification submission needs. This is the anchor deliverable of the multi-year relationship, contingent on the shared scoping outcomes above.
MVP demoed at Waypoints kickoff · October 5, 2026
A controlled synthetic testbench for the clinical-evaluation methodology — not a training product, not a diagnostic, not a therapeutic, and not a substitute for the evaluation itself. Two artifacts:
- Adult-PTSD state simulator (three canonical archetypes). Software characters with persistent state and deterministic replay covering combat PTSD, moral-injury PTSD, and TBI-comorbid PTSD. Lets Mayo faculty inspect the evaluation methodology — perturbation schedules, longitudinal cadence, uncertainty-handling behavior — end-to-end before any patient time, DUA, or IRB effort is committed.
- CNSR-Panel input-reference calculation stack. Running today on Scyla, ready to be pointed at Mayo-curated real inputs once the prospective evaluation is scoped.
These artifacts are the front of the clinical-evaluation relationship, not the relationship itself.
Downstream (after the clinical-evaluation record supports it)
- CDER COA Qualification of NeXus AI ART. Letter of Intent v11 submitted July 11, 2026 under §507 of the Federal Food, Drug, and Cosmetic Act (21st Century Cures Act §3011). Qualification Plan drafted Q4 2026 following LOI acceptance, per the four measurement principles from the CDER COA Qualification Program Standard of Evidence.
- Phase 2 pharmacotherapy trial site. Mayo as trial site adopting ART as hierarchically-ordered secondary endpoint measuring the treatment-emergent DSM-5 Criterion E arousal-and-reactivity trajectory. This is a later-stage relationship, appropriate to open once the clinical-evaluation record supports it. Elder Granger MG (Ret.) MD (invited to the NN Board of Directors) opens the DoD and TRICARE veteran-recruitment channel that most academic trial sites cannot access.
- Sequenced expansion. Once the PTSD clinical-evaluation record exists, adjacent state-transition indications (substance-use recovery, psychiatric pharmacotherapy response monitoring, adult multimorbidity longitudinal state) reuse the same AetherProtocols architecture against the same evaluation methodology.
Application answers, Page 1 of 4 · PLACEHOLDER DRAFTS
Drafts only. Marjorie will fine-tune in the actual form, route through Jason, and submit personally.
1 · Job title / role
Marjorie McCubbins, BSc Biochemistry and Molecular Biology, MHA candidate (Grand Canyon University), four years clinical healthcare experience. Founder & CEO; Acting COO of NeXus NeuroInformatics, Inc. (the submitting entity). Founder & CEO of Nexus Concordat, Inc. (the parent brand and IP-holding entity that licenses the four patents into NN).
2 · Leadership team
- Marjorie McCubbins, BSc · Founder & CEO; Acting COO, NeXus NeuroInformatics, Inc. Founder & CEO, Nexus Concordat, Inc. Sole inventor on 63/939,190 and 63/988,485; co-inventor with Aislinn on 63/962,385 and 64/034,536.
- Major General Elder Granger, MD, USA (Retired) · NeXus NeuroInformatics Board of Directors (seat in process). Former Deputy Director and Program Executive Officer, TRICARE Management Activity; oversaw a $22.5 billion Defense Health Program covering 9.2 million service members, families, and retirees. Former Commander, Task Force 44th Medical Command and Command Surgeon for Multinational Corps Iraq. Credentials: ACRP-CP, CHC, NACD Directorship Certification. Owner of THE 5Ps, LLC, a Service-Disabled Veteran-Owned Small Business. Chief Medical Advisor at MedSync Corp.
- Jason Alba, MBA, DBA · Board Director, anchor SAFE investor, and alternate point of contact on the CDER COA-Q submission. Founder of EvoSynapse AI. Signed the late-fusion multimodal architectural choice for NeXus AI ART in writing: "isolates the data from the engine."
- Aislinn McCubbins · Director, NeXus NeuroInformatics, Inc.; Co-inventor of record on U.S. Provisionals 63/962,385 and 64/034,536. Separately serves as COO of Dynamic Hallucination, Inc. (the entertainment sister subsidiary; separate revenue channel, not part of this application).
- Shailee Desai · Manager of Quality Compliance, NeXus NeuroInformatics. MS Regulatory Affairs candidate at Northeastern University. Owns the Design History File under 21 CFR 820.30, IEC 62304, IEC 82304. Building the design-control system.
External regulatory consultation is retained as needed.
3 · Company website
patent.nexusconcordat.com (architectural and IP documentation)
nexusneurodata.com (NN clinical/regulatory surface)
ptsd.nexusneurodata.com/slr (systematic literature-review framework drawing on peer-reviewed evidence)
4 · Pitch deck / executive summary
The top of this page is the canonical one-page summary for export. Print to PDF and upload.
5–10 · Company address
NeXus NeuroInformatics, Inc. · 614 County Highway 325 · Hamilton, AL 35570-4078 · USA
11 · Healthcare sector(s)
- ✅ Digital Health (primary · deterministic longitudinal state-computation architecture serving clinical evaluation)
- ✅ Clinical Trials (later-stage · downstream Phase 2 trial-site adoption once evaluation record supports it)
- ☐ Medical Devices (intentionally avoided at this MVP · CDS positioning under FDA Jan 29, 2026 guidance)
- ☐ Diagnostics (not a diagnostic tool)
- ☐ Therapeutics (not a therapeutic)
12 · Problem addressed
In PTSD pharmacotherapy drug development, treatment response, decompensation, and adverse-event windows unfold over days to weeks, in signals that are longitudinal and coupled — not in single-timepoint snapshots. Clinical trialists, drug-development sponsors, and translational researchers lack a way to observe an individual participant’s physiological-and-clinical state as a coherent trajectory, with uncertainty, at the resolution required to characterize investigational pharmacotherapy effects. AetherProtocols computes that trajectory. The open question — and the reason we are approaching Mayo — is whether the trajectories it produces correspond to clinically meaningful change in real adults with established PTSD under study conditions. Patient-care decision support is explicitly out of scope for the first use; that framing can be revisited only if and when evidence and regulation support it.
13 · Roles typically using / benefiting from the solution
- Trial investigators running PTSD pharmacotherapy Phase 2 and Phase 3 studies
- Sponsor analysis teams characterizing longitudinal treatment-response and adverse-event trajectories in investigational-pharmacotherapy data
- Translational researchers studying longitudinal state dynamics in PTSD populations under research-protocol conditions
- Regulatory reviewers evaluating COA instruments intended as hierarchically-ordered secondary endpoints
- Clinical research staff at academic medical centers running longitudinal-evaluation protocols
14 · Roles typically purchasing the solution
- Pharmaceutical sponsors running Phase 2/3 PTSD pharmacotherapy trials (COA instrument licensing)
- Academic medical center clinical-research offices adopting the evaluation methodology
- Federal / DoD / VA clinical-research pipelines targeting veterans’ PTSD (Elder Granger MG (Ret.) channel)
15 · Competitors
We have not identified a directly comparable platform offering a deterministic longitudinal state-computation architecture with the state-persistence-and-decay invariants above, protected by a hash-verifiable specialist composition layer, in a form intended for clinical evaluation as a hierarchically-ordered COA secondary endpoint; a formal competitive landscape review is a scheduled activity, not yet complete. Adjacent categories we are aware of include wearables-driven remote patient monitoring (e.g., Biofourmis, CopilotIQ) and clinician-facing AI decision support (various vendors); to our current knowledge, these do not position a deterministic-state claim or design themselves to be evaluated against clinical-state trajectories as a primary evaluation object, but that observation is subject to revision as the landscape review completes.
Application answers, Page 2 of 4 · PLACEHOLDER DRAFTS
Drafts only. Marjorie will fine-tune in the actual form, route through Jason, and submit personally.
16 · Describe your innovation. How is it differentiated?
AetherProtocols is a deterministic longitudinal state-computation architecture. Given qualified observations from AetherAnalyte, it computes an individualized, uncertainty-bearing state trajectory that persists across sessions, decays across observation gaps, and does not confuse absence-of-signal with recovery. That is the innovation. It is differentiated from every AI wrapper and remote-monitoring platform in the field by three properties: (a) determinism at the state layer (learned interpretation is downstream, in the NLM); (b) uncertainty as a first-class output, not a post-hoc annotation; (c) architectural — not learned — decay behavior that makes the trajectory clinically interpretable rather than statistically smoothed.
17 · What evidence do you have that it works?
The evidence separates cleanly into three lanes; conflating them dissolves the argument, so we keep them explicit.
Lane A — State-computation substrate (evidence that the deterministic longitudinal state layer runs). The AetherProtocols state-computation architecture is not vaporware and not a slideware claim. It operates today as an executable substrate on our internal engineering runtime, with the full canonical stack (twelve layers, L0–L11) exercised end-to-end and under continuous engineering audit since April 2026. The state layer is coupled at runtime to a durable state store (PostgreSQL) and a graph-neighbor query layer (Neo4j) through a bridge module, so state persistence and decay are exercised operationally, not merely specified. All architectural artifacts (Scyla programs, executable canon stack, hash-verifiable specialist manifests, ARCHITECTURE and CURRENT_STATE engineering records) are available under mutual NDA. This is the evidence that the state layer produces state trajectories at all; whether those trajectories correspond to within-person clinical reality is precisely the question this application is asking Mayo to help evaluate.
Lane B — Downstream NLM training pipeline (evidence that the learned interpretation layer trains). A live specialist cell (cardiac_gen3) serves inference behind a signed manifest verifiable by SHA-256 at nexusneurodata.com/cell-demo.html. This is evidence that our NLM (downstream learned interpretation) training pipeline works, not evidence that the state layer tracks clinical reality. We label it explicitly here to avoid the common overclaim.
Lane C — Regulatory, evidentiary, and institutional posture. Four USPTO provisional patents on file (63/939,190; 63/962,385; 63/988,485; 64/034,536); non-provisional consolidation in preparation under The Architecture of the Digital Mind. Systematic literature-review framework drawing on peer-reviewed evidence to constrain the CNSR-Panel biomarker inputs: formal SLR Protocol v1.6 (committed July 12, 2026) live at ptsd.nexusneurodata.com/slr. CDER COA Qualification LOI v11 submitted July 11, 2026 under §507 FD&C Act. FDA U01 GRANT14747560 submitted 2026-08-20 (currently in Pre-Award Risk Assessment per Sept 10, 2026 correspondence). NIH Transformative R01 GRANT14753616 submitted 2026-09-03. NIH SBIR PA-27-100 R43 submitted 2026-09-08. Advisory infrastructure: Jason Alba (Board Director + anchor SAFE), Elder Granger MG (Ret.) MD (Board seat in process, DoD/TRICARE credibility), Shailee Desai (Manager of Quality Compliance, DHF discipline). External regulatory consultation retained as needed.
18 · What Mayo capabilities complement the innovation?
Our existing federal research programs test implementation fidelity (FDA U01), population-level correspondence against reference biomarker panels (FDA U01 Aim 3 observational cohort), and counterfactual robustness against synthetic profiles (NIH Transformative R01). The unresolved question is whether AetherProtocols' individualized state trajectories correspond to real within-person biological and clinical state transitions over time. Mayo is uniquely positioned to help close that gap.
Specifically, Mayo may provide access to the longitudinal clinical and biological observations needed to establish within-person longitudinal ground truth under an appropriate study design — paired with the psychiatric and clinical-trials expertise required to interpret those observations correctly in adult PTSD. The five categories mapped above (clinical study design, longitudinal data access, PTSD expertise, biomarker / endpoint interpretation, prospective validation) all serve that single validation objective. Mayo Clinic Platform_Discover and the broader Mayo longitudinal-data infrastructure are cited as illustrative examples of Mayo's institutional capability. Specific dataset selection and access mechanisms are design outputs of the joint prospective-evaluation protocol, not design inputs assumed here.
19 · What is your intellectual-property posture?
Four USPTO provisional applications currently on file; non-provisional consolidation in preparation under The Architecture of the Digital Mind. NN operates the clinical/regulatory work under an executed exclusive-license agreement from Nexus Concordat, Inc. (parent, IP holder). Scyla execution/compiler layer wholly owned by NN.
Application answers, Page 3 of 4 · PLACEHOLDER DRAFTS
Drafts only.
20 · Milestones over the past 12 months
- September 8, 2026. NIH SBIR PA-27-100 R43 submitted (NN as SBC applicant).
- September 3, 2026. NIH R01 (Transformative, RFA-RM-27-003) submitted — GRANT14753616.
- August 20, 2026. FDA U01 (RFA-FD-26-012) submitted — GRANT14747560. Currently in FDA Pre-Award Risk Assessment (correspondence received Sept 10, 2026).
- August 2026. Executed mutual NDA with our Track-1 analytical/assay-validation partner (partner not identified at this stage; identification available under complementary Mayo NDA).
- July 12, 2026. Peer-reviewed SLR Protocol v1.6 committed. Live at ptsd.nexusneurodata.com/slr.
- July 11, 2026. CDER COA Qualification LOI v11 submitted for NeXus AI ART under §507 FD&C Act.
- June–July 2026. NeXus NeuroInformatics, Inc. formed as operating clinical company. UEI TMUCA7QGRNA7. EIN 42-3415697. Executed exclusive-license agreement from Nexus Concordat, Inc.
- April–May 2026. Four USPTO provisional applications filed (63/939,190; 63/962,385; 63/988,485; 64/034,536).
21 · Milestones over the next 12 months
- September 20, 2026. Waypoints application submitted.
- Late September 2026. FDA PRA questionnaire response filed (U01 pre-award review).
- October 5, 2026. Waypoints kickoff. MVP demo (adult-PTSD state simulator + CNSR-Panel calculation stack).
- Q4 2026. If Waypoints-selected: joint clinical-evaluation protocol scoping with Mayo psychiatry / clinical-trials faculty. CDER COA-Q Qualification Plan drafted following LOI acceptance.
- Q1–Q2 2027. Prospective clinical-evaluation study design finalized, IRB pathway determined, DUA scoped, dataset selection follows protocol design.
- By December 2026. Non-provisional patent consolidation filed under The Architecture of the Digital Mind ahead of the earliest provisional’s 12-month statutory deadline.
- Q3–Q4 2027. Prospective clinical-evaluation study opens at Mayo (design permitting).
Application answers, Page 4 of 4 · PLACEHOLDER DRAFTS
Drafts only.
22 · What kind of Mayo engagement would be most valuable?
A structured Waypoints engagement leading into a joint prospective-evaluation protocol with Mayo psychiatry / clinical-trials faculty, anchored on a single question: does the AetherProtocols state trajectory correctly track a real individual's real state dynamics over time in adult PTSD?
Concretely, the sequence we would ask Mayo to help us walk:
- Faculty introductions. Mayo faculty with active adult-PTSD clinical or research practice, and interest in longitudinal state-trajectory methodology.
- Joint protocol scoping. Prospective-evaluation protocol designed against the five-category ask above, with within-person longitudinal ground truth as the primary evaluation object.
- Data and access determination. Joint determination of which Mayo longitudinal data assets and access mechanisms (retrospective and/or prospective) can support the ground-truth granularity the evaluation requires, and the appropriate IRB pathway. This is a design output, not an ask for pre-existing bulk data.
- Execution. A jointly designed prospective evaluation with an appropriate Mayo clinical research team, subject to agreement, IRB review, data permissions, and funding — the study that closes the loop from state trajectory to individual-level clinical reality and produces the record the downstream CDER COA Qualification submission needs.
23 · What are you NOT asking Mayo to do?
We are not asking Mayo to build our AI, train our AI, provide data as training input, provide standardized-patient actor programs, run a residency-training product, or serve as primary regulatory counsel. AetherProtocols is our architecture. The clinical evaluation of its state trajectories is the collaboration.
24 · What is the funding posture?
NeXus NeuroInformatics, Inc. is self-funded plus $2,500 anchor SAFE from Jason Alba. Non-dilutive tracks in flight include FDA U01, NIH R01, NIH SBIR R43, and NSF SBIR resubmission. Institutional legal-and-regulatory engagement spend is not budgeted at this stage; a Mayo collaboration would trigger a separate scoping conversation.
25 · Supporting materials attached
- Executive summary PDF (exported from the top of this page)
- Team credential summary PDF: Marjorie (chemistry + MHA + CEO), Elder Granger (TRICARE Deputy Director + Iraq combat medical command + NACD), Aislinn (co-inventor), Jason (Board + SAFE), Shailee (Quality Compliance)
- Patent portfolio summary (four provisionals, consolidation in preparation)
- Peer-reviewed SLR: ptsd.nexusneurodata.com/slr
- Live specialist cell demo: nexusneurodata.com/cell-demo.html
Deadlines & next steps
- Application deadline: September 20, 2026.
- Selection decisions: ~September 28, 2026 (~8 days after submission).
- Program kickoff (if selected): October 5, 2026 — MVP demo, initial Mayo faculty introductions.
- Formal partnership documentation (LOI / MOU / RCA): flows after Waypoints selection, Q4 2026 through Q1 2027.
- Prospective evaluation study open: targeted Q3–Q4 2027 (design-permitting).