𝛼-CD20 x 𝛼-CD40

A Deceptively Simple Idea with Profound Implications

CD20 & CD40 are validated powerful upstream targets on pathologic B & T cells, but simultaneous targeting remains unexplored due to theoretical safety concerns of dual inhibition

Scientific Evolution

By pursuing the hard problem of transplantation tolerance, Diabetes Free, Inc. (DFI) has arrived at potentially disruptive solutions to the big problems in autoimmunity and oncology

First, DFI induced immune tolerance to Islet Transplantation as a functional cure of diabetes

Antigen Presenter x 𝛼-CD40

=

Immune Tolerance

Now, DFI is applying its transplantation rigor to autoimmunity & oncology

𝛼-CD20 x 𝛼-CD40

=

Immune Reset

Evolution of Immunomodulation Immune Reset

𝛼-CD20 x 𝛼-CD40 BsAb

	1st Generation B cell Depletion CD19/CD20	2nd Generation CD19 CAR-T	3rd Generation T cell Engagers CD19/20xCD3	Next Generation 𝛼-CD20 x 𝛼-CD40 BsAb
clinical outcome	Delayed Progression	Remission	Partial Remission	Curative Intent
safety			(csr)
circulating B cells depletion
tissue B cells depletion	—
memory B cells depletion	—
tcells: Tregs ˄	—	—	—
tcells: Teff ˅	—	—	—
macrophage / APCs depletion	—	—	—

Immune Reset Curative Intent

Requires Both Humoral & Cellular Immunomodulation

Pan Autoimmune Indication Strategy

BsAb mechanism could address several large autoimmune indications

Largest Autoimmune Indication TAMs

Rheumatoid Arthritis

Psoriasis

Multiple Sclerosis

Other

UC & Crohn's Disease

Atopic Dermatitis

T1D

Psoriatic Arthritis

Legend

BsAb

𝛼-CD40

IND-enabled / submitted

Potential / BsAb Indication

Oncology Rationale

IMMUNE CLEARANCE of Malignant B cell Compartment

Loss of CD19/20 is a common escape mechanism, but co-expression of CD20 and CD40 may result in superior tumor clearance

CD20 CD40 co-expression in leukemias & lymphomas

	CD20	CD40
DLBCL	High	High
CLL	Weak to Moderate	Moderate
Burkitt Lymphoma	High	High
Follicular Lymphoma	High	High
Marginal Zone Lymphoma	High	High
Mantle Cell Lymphoma	High	Moderate to High

Pipeline

	Therapy	Indications	Status
	Monoclonal mAb 𝛼-CD40	Transplantation & MS	IND Enabled
	Bivalent BsAb1 𝛼-CD40 x 𝛼-CD20	Autoimmunity (RA, SLE, Sjögren's)	FIH Q4 2025
	Tetravalent BsAb 𝛼-CD402 x 𝛼-CD202	Oncology (FL, MZL, MCL)	FIH Q1 2026

Legend

𝛼-CD20

𝛼-CD40

1. IP 2045 CoM

NB: Antibody graphics not representative of actual structure