Altor's Product Pipeline by Technology

Class
Products
Description
Status
Antibody
Therapeutics
ALT-836
(partnered with Genentech)
anti-Tissue Factor antibody for
treating ALI/ARDS
Phase II (Completed)
anti-Tissue Factor antibody for
treating Cancers
Phase I/IIa (Completed)
TCR
Therapeutics
ALT-801
p53-TCR/IL-2 fusion protein for
treating Metastatic Melanoma
Phase Ib/II (Completed)
Locally-Advanced / Metastatic
Bladder Cancer
Phase II
Non-Muscle Invasive Bladder Cancer
Phase II
Multiple Myeloma
Phase II
Donor lymphocyte infusion to treat
Acute Myeloid Leukemia
Phase I/IIa
ALT-802
p53-TCR/IgG1 fusion protein for
treating Non-Small Cell Lung Cancer
Preclinical
ALT-804
p53-TCR/IL-15 fusion protein for
treating Cancer
Preclinical
Antiviral TCR–Ck Fusions
Antiviral TCR–Ig Fusions
TCRs targeted to antigens derived
from HIV, HCV and CMV
Preclinical
IL-15
ALT-803
Metastatic Melanoma
Phase I/II
Relapse of Hematologic Malignancies after ASCT
IND
Multiple Myeloma
Preclinical
Reagents
STAR™ Multimers
Multimeric TCR reagents for research
Marketed;
Available for purchase

Altor’s STAR™ Technology

T-cells are essential components in the human body’s initiation and maintenance of immune responses against infectious agents and foreign cells such as cancer. Two sets of proteins, the major histocompatibility complex (MHC) molecules and the T-cell receptors (TCR), play a central role in controlling T-cell responses. The MHC molecules on the surface of antigen-presenting cells display protein fragments (called peptide antigens) derived from foreign agents and cellular proteins. TCRs on the surface of T-cells recognize and bind to specific peptide antigens displayed by the MHC molecules. In viral infection and cancer, TCR recognition of viral and tumor antigens signals the T-cells to react against the diseased cells. However, TCR recognition of antigens on normal cells can lead to the aberrant immune responses associated with autoimmune disease, allergies and graft rejection.


STAR™ (Soluble T-cell Antigen Receptor) / STAR™ Fusion

This unique proprietary STAR™ technology has allowed Altor to produce biologically active, soluble TCR molecules in a single-chain format. Combined with its Fusion technology, Altor is able to produce STAR™ fusion reagents that retain the ability of the TCR to specifically recognize novel targets on virus-infected or cancerous cells, including intracellular antigens that are not accessible to therapeutic antibodies...

More on STAR™ Fusion Technology...


STAR™ Multimers

For technical and order information on research reagents...


STAR-IMPACT™ (Inhibitor of MHC-Peptide Activation of T-cells) Screening)

Novel TCR and MHC-peptide production techniques have allowed Altor to assemble highly sensitive screening methods to identify compounds that block TCR interaction with the MHC-peptide complex involved in immune disorders. Of particular interest is the isolation of MHC antagonists that inhibit the activity of autoimmune disease-associated HLA molecules, such HLA-DR2 and HLA-DR4. Using these methods, Altor has established proof-of-concept that non-toxic chemical compounds can be isolated that specifically block TCR:HLA-peptide interactions as well as HLA-restricted T-cell responses in vivo. Altor is seeking partnership opportunities for development of these technologies and product candidates.

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Tissue Factor Antagonist Technology

Tissue factor (TF) is a membrane protein that initiates the extrinsic coagulation pathway, with important additional roles in tumor growth, angiogenesis, and systemic inflammation. There is an abundance of published evidence that coagulation and inflammation processes are closely related in the pathology of acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS), sepsis and tumor metastasis, suggesting that TF antagonists could be effective in treating these diseases. Numerous studies conducted at Altor using ALT-836, its proprietary anti-tissue factor antibody, and at other laboratories, employing other TF antagonists, have confirmed these suggestions.

More on Tissue Factor Antagonist Technology (PDF)...

IL-15 Protein Superagonist and Scaffold Technology

Interleukin-15 (IL-15) is related to interleukin-2 (IL-2) and is a critical factor for the development, proliferation and activation of effector natural killer (NK) and CD8+ memory T cells. However unlike IL-2, IL-15 does not promote activation-induced cell death and supports long lasting CD8+ T cell memory and effector responses against diseased cells, suggesting that IL-15 may be superior to IL-2 as an immunotherapeutic for the treatment of cancers. A recent National Cancer Institute (NCI) review listed IL-15 as the most promising product candidate among twelve immunotherapy drugs that could potentially cure cancer. IL-15 has a novel mechanism of action in which IL-15 and IL-15 receptor α (IL-15Rα) are coordinately expressed by antigen-presenting cells (monocytes and dendritic cells), and IL-15 bound to IL-15Rα is presented in trans to neighboring NK or CD8+ T cells expressing only the IL-2Rβγ receptor.

Altor has developed a technology to improve the binding ability of IL-15 to its receptor IL-2Rβγ by substituting the amino acid residue asparagine to aspartic acid at the position 72. This amino acid substitution, known as N72D, significantly enhances the binding of IL-15 to its receptor IL-2Rβγ. More importantly, the N72D substitution also increases the biological activity of IL-15 four to five fold. Thus, ALT-803 is a fusion complex of the IL-15N72D mutein with an IL-15Rα-IgG1 Fc.

Altor has demonstrated that ALT-803 treatment can provide durable and protective immune cell-mediated responses in several mouse models of multiple myeloma. Pharmacokinetic and pharmacodynamic studies verified that the ALT-803 complex has a significantly longer half-life and also increased potency in stimulating NK and T cell responses when compared to IL-15. The enhanced activity of ALT-803 is likely the result of a combination of the increased binding activity of the N72D mutein to the IL-15Rβγ complex, optimized cytokine trans-presentation by the IL-15Rα chain in vivo (through the FcR receptors on dendritic cells and macrophages), the dimeric nature of the cytokine domain (increased avidity to IL-15Rβγ) and its increased in-vivo half-life compared to IL-15 (25 h vs. <40 min).

Altor has also exploited the high-affinity interactions between IL-15 and the extracellular IL-15Rα sushi domain (IL-15RαSu) to create a functional scaffold for the design of multi-specific fusion protein complexes. Using single-chain T cell receptors (scTCRs) and antibody as recognition domains linked to the IL-15:IL-15Rα scaffold, Altor has generated both bivalent and bispecific complexes. In these fusions, the scTCR and antibody domains retain the antigen binding activity and the IL-15 domain exhibits receptor binding and biological activity. Together, these properties indicate that the IL-15 and IL-15RαSu domains can be used as versatile, functional scaffold for generating novel targeted immune molecules.

Novel IL-15 antagonists have also been identified that nonproductively occupy the IL-15βγ receptor that could be useful as immunosuppressive agents for autoimmune disease.

More on IL-15 Technology (PDF)...

Literature and Publications...