ExoBiotic Therapeutics: CLL Therapy Reimagined

Founder Team: Simran Shergill, Prableen Dhugga, Prabjot Dhugga, Hadia Shaikh, Harjind Sarao, Iman Haider
Project Focus: Novel two-pronged approach for treating Chronic Lymphocytic Leukemia (CLL)

Detection Issues: Lack of early-stage, accessible methods for detecting CLL.
Treatment Precision: Current treatments are non-targeted, resulting in off-target effects and unintended damage to healthy cells.

Diagnostic Tests: Development of a novel diagnostic to enhance early intervention in CLL cases.
Liposomes: Use of modified CLL-targeted lipoprotein nanoparticles for improved treatment precision.
Therapeutic Approaches:
- Incorporation of DNAzymes for targeted RNA cleavage in cancer cells.
- Utilization of bacterial-based therapies for enhancing drug delivery.

Develop Quick Diagnostics: Innovate efficient diagnostics for early CLL detection.
Innovative Therapeutics: Create optimized liposome-based drugs to decrease off-target effects.
Combination Therapies: Test various payload combinations to identify effective therapeutic strategies.
Commercialization Goal: Conduct necessary clinical trials and secure regulatory approval for market introduction.

Description: A slow-growing blood cancer arising from monoclonal B cell proliferation, accounting for approximately one-third of all leukemia cases.
Diagnosis Criteria: Requires a minimum of 5x10^9 circulating B lymphocytes per liter of blood. Typical surface markers include CD5+, CD19+, and CD23+.

T-Cell Independent and Dependent Pathways: CLL cells have complex migration patterns influenced by both immune evasion and activation across various body compartments, particularly bone marrow and lymph nodes.
- Key Oncogenic Events: Include BCR signaling, genetic changes, and microenvironmental factors.

Incidence: Higher rates of CLL in males and older adults (ages 65-70).
Market Growth: Market size projected to grow from $14.41 billion (2024) to $22.05 billion (2029), driven by advancements in CLL understanding and demographic shifts.

Biomarker Test: A dual-cassette lateral flow assay for rapid CLL screening, requiring a small blood sample.
Key Biomarkers:
- Surface Antigens: CD5+, CD19+, CD23+ (characteristic of CLL).
- Soluble Biomarker: Beta-2-microglobulin (β2-M) correlates with disease progression and is secreted due to excessive B-cell turnover.
- Lateral Flow Test Lines: Quality control based on specific antibody-antigen concentrations to evaluate healthy vs. at-risk patients.

Salmonella typhimurium (VNP20009): Engineered to induce apoptosis in leukemia cells.
Mechanism: Targets cancer cells, demonstrated potential synergy in inducing tumor cell death through in vitro and in vivo studies.

Functionality: Catalytic DNA sequences that target and cleave specific RNA molecules, particularly anti-apoptotic genes BCL-2 and MYC.
Benefits: Multi-target inhibition to prevent therapeutic resistance seen with single drug therapies.

Targeting CLL Cells: Difficulty in accessing protected niches such as lymph nodes and bone marrow.
Liposome Design: Employing strategies like PEGylation for immune evasion and utilizing chemokine receptors for precise homing to CLL cells.
Testing and Verification: Validate therapeutic efficacy and targeting through in vivo models and clinical trials.

Clinical Trials: Phase I for safety, moving towards comparative efficacy in Phase II and long-term effectiveness in Phase III trials.
Commercialization Timeline: Steps planned for IND submission, trial assessments, and securing approvals within a decade.
Funding Goals: Aim for ~$2 million to support early-stage research, trials, and regulatory procedures.

To radically improve diagnosis and treatment for CLL, leveraging innovative diagnostics and targeted therapeutic strategies to enhance patient outcomes and precision medicine in cancer treatment.