Class		Products	Description	Status
Antibody Therapeutics		ALT-836 (partnered with Genentech)	anti-Tissue Factor Antibody for treating ALI/ARDS	Phase II
			anti-Tissue Factor Antibody for treating cancers	Phase I/IIa
TCR Therapeutics		ALT-801 (IV Bolus Injection)	p53-TCR/IL-2 fusion protein for treating metastatic melanoma	Phase Ib/II
			Locally-advanced / metastatic bladder cancer	Phase Ib/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	Non-targeted IL-15 super agonist/IL- 15Ra-Fc fusion complex for treating solid and hematogical tumors	Pre-IND
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 have 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 Altor has found that multimeric forms of the STAR™ molecules can be used to evaluate peptide antigen presentation, in the context of MHC molecules, on cancer cells and tissues, and that staining methods employing these reagents have utility in validating and quantifying tumor and viral antigen presentation and in the design and optimization of vaccine-based approaches. As a result, the Company has launched a line of first-in-class research reagents that will allow investigators to gain a better understanding of cancer and viral infection, potentially leading to the development of new diagnostic and therapeutic approaches. In addition, Altor is using STAR™ Multimer staining methods in its clinical development strategy to identify patients most likely to benefit from TCR-based targeted immunotherapy. 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. More on STAR-IMPACT™ Technology...
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... IL-15 Protein Scaffold Technology Interleukin-15 (IL-15) is related to IL-2 and is a critical factor for the development, proliferation and activation of effector natural killer (NK) and CD8+ memory T cells. IL-15 inhibits IL-2-induced AICD and supports long lasting CD8+ T cell memory and effector responses against diseased cells, suggesting that IL-15 may be superior to IL-2 for the treatment of cancers. Indeed, a recent 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-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. As a co-stimulatory event occurring at the immunological synapse, IL-15 trans-presentation appears to be a dominant mechanism for IL-15 action in vivo and appears to play a major role in tumor immunosurveillance. Altor has developed a novel IL-15 superagonist complex, designated ALT-803, with increased ability to bind IL-2Rβγ and enhanced biological activity. This IL-15 super agonist complex has highly potent IL-15 activity in vitro and in vivo and is in testing for use locally (i.e. intravesical administration) in treating patients with non-muscle invasive bladder cancer (NMIBC). Altor has also exploited the high-affinity interactions between hIL-15 and the extracellular hIL-15Rα sushi domain (hIL-15RαSu) to create a functional scaffold for the design of multi-specific fusion protein complexes. Using single-chain T cell receptors (scTCRs) as recognition domains linked to the IL-15:IL-15Rα scaffold, we generated both bivalent and bispecific complexes. In these fusions, the scTCR domains retain the antigen binding activity and the hIL-15 domain exhibits receptor binding and biological activity. Together, these properties indicate that the hIL-15 and hIL-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...

Literature and Publications...