SCF DISCOVERY PHASE WORKFLOW INITIATION | Antigen-Ranking Engine (SCF-ARGEN-HTT-NO-01)

PROJECT HELIX-HTT | Huntington’s-Adjacent Neuro-Oncology Vaccine Program

INITIATION STATUS

Program Status: INITIATED

Workflow Phase: Discovery Phase (Phase I)

Program Code: SCF-ARGEN-HTT-NO-01

Execution Level: Research & Platform Development

Output Goal: Ranked Antigen Candidate Library for Therapeutic Vaccine Design

PHASE I — DISCOVERY PHASE ACTIVATION

The Discovery Phase consists of six sequential workstreams:

WS-1: Biospecimen & Data Acquisition
        ↓
WS-2: Multi-Omics Characterization
        ↓
WS-3: Antigen Discovery Pipeline
        ↓
WS-4: SCF Microenvironment Intelligence Layer
        ↓
WS-5: Antigen Ranking Engine
        ↓
WS-6: Vaccine Candidate Assembly

WORKSTREAM 1 (WS-1)

BIOSPECIMEN & DATA ACQUISITION

Objective

Generate the foundational dataset required for vaccine discovery.

Required Biospecimens

Tumor Material

Priority order:

Fresh tumor tissue
Frozen tumor tissue
FFPE tumor tissue

Matched Normal Control

Priority order:

Peripheral blood
Buccal swab
Normal tissue

Purpose:

Germline subtraction
Mutation identification

Optional Samples

Sample	Purpose
Plasma	ctDNA
CSF	CNS biomarkers
PBMC	Immune profiling
Tumor lysate	Immunopeptidomics

Deliverable

D-WS1-001

Multi-Omics Biospecimen Registry

WORKSTREAM 2 (WS-2)

MULTI-OMICS CHARACTERIZATION

Module A

Genomics

Generate:

Somatic mutations
Structural variants
Indels
Fusion events

Output:

Mutation Catalog (MCAT)

Module B

Transcriptomics

Generate:

Gene expression
Alternative splicing
Fusion expression

Output:

Expression Atlas (EXAT)

Module C

HLA Profiling

Generate:

HLA-A
HLA-B
HLA-C
DR
DQ

Output:

HLA Compatibility Matrix (HCM)

Module D

Immunopeptidomics

Generate:

Naturally presented peptides
HLA-associated peptide inventory

Output:

Presented Antigen Library (PAL)

Deliverable

D-WS2-001

SCF Multi-Omics Integration Dataset

WORKSTREAM 3 (WS-3)

ANTIGEN DISCOVERY PIPELINE

Step 1

Identify:

Personalized Neoantigens

Examples:

SNVs
Indels
Fusions
Splice variants

Output:

Neoantigen Candidate Pool (NCP)

Step 2

Identify:

Tumor Associated Antigens

Output:

TAA Candidate Pool

Step 3

Identify:

SCF Experimental Antigens

Including:

DNA repair stress peptides
Hypoxia-associated peptides
Neuroimmune stress peptides

Output:

SCF Antigen Pool

Deliverable

D-WS3-001

Master Antigen Inventory

WORKSTREAM 4 (WS-4)

SCF MICROENVIRONMENT INTELLIGENCE

RHENOVA Layer

Assess:

Hypoxia

Markers:

HIF-1α
CAIX
VEGF

Redox Biology

Markers:

8-OHdG
MDA
GSH:GSSG

Immune Access

Markers:

CD8
IFNγ
CXCL9
CXCL10

Microglial State

Markers:

IBA1
TREM2
TNFα
IL1β

Output

SCF Microenvironment Suitability Score
(SCF-MES)

Deliverable

D-WS4-001

Microenvironment Intelligence Report

WORKSTREAM 5 (WS-5)

ANTIGEN RANKING ENGINE

Antigen Priority Score

APS =
Tumor Specificity
+
Expression
+
HLA Presentation
+
Immunopeptidomics
+
Clonality
+
SCF-MES

-
CNS Risk
-
Immune Escape Risk

Ranking Classes

Class	Meaning
A	Include
B	Backup
C	Exploratory
X	Exclude

Deliverable

D-WS5-001

Ranked Antigen Candidate Library

WORKSTREAM 6 (WS-6)

VACCINE CANDIDATE ASSEMBLY

Tier 1 Selection

Select:

8–20 Primary Antigens

Requirements:

APS ≥ 80
CNS Risk Low
HLA Coverage Adequate

Tier 2 Selection

3–5 Backup Antigens

Tier 3 Selection

1–3 Experimental SCF Antigens

Research Use Only

Deliverable

D-WS6-001

SCF Vaccine Candidate Package

PROJECT HELIX-HTT DISCOVERY PHASE OUTPUTS

Upon completion, the Discovery Phase will generate:

Core Deliverables

Multi-Omics Dataset
Mutation Catalog
Expression Atlas
HLA Compatibility Matrix
Presented Antigen Library
SCF Microenvironment Report
Ranked Antigen Candidate Library
Vaccine Candidate Package

DECISION GATE (DG-1)

Advancement Criteria

Advance to Preclinical Vaccine Development if:

≥10 Class-A antigens identified
Immunopeptidomics confirmation achieved
CNS cross-reactivity risk acceptable
SCF-MES ≥ predefined threshold
No dominant immune-escape signature

NEXT PHASE

Phase II: Preclinical Vaccine Development

Will include:

Vaccine Construct Design
Adjuvant Selection Strategy
Dendritic Cell Activation Studies
T-Cell Activation Assays
Tumor Killing Assays
Neuroimmune Safety Assessment
IND-Enabling Vaccine Pharmacology Package

SCF STRATEGIC VALUE

This initiation formally establishes the discovery infrastructure necessary to move from:

Tumor Biology → Antigen Discovery → Vaccine Design → IND-Enabling Development

while integrating:

Multi-omics intelligence
Neuro-oncology immunology
RHENOVA microenvironment mapping
SCF-PCR therapeutic design principles
Personalized vaccine development workflows.