Altor's Product Pipeline

Product
Indication
Preclinical
IND
Phase I
Phase II
Phase III
ALT-801
Advanced Bladder Cancer
Non-Muscle Invasive Bladder Cancer
ALT-836
ALI/ARDS
Solid Tumors
ALT-803
Metastatic Melanoma
Hematologic Malignancy
Multiple Myeloma
Non-Muscle Invasive Bladder Cancer

Clinical Development

The Company currently has the following three products in clinical trials:

ALT-801

Altor’s long-term clinical objective is to develop ALT-801, a p53-specific scTCR/IL-2 fusion protein, as a targeted immunotherapeutic with better antitumor potency, a lower toxicity profile and more convenient dosing schedule compared with that of human recombinant IL-2. The Company has completed an open-label, dose-escalating Phase I/IIa clinical trial (Clinical Trials.gov Identifier: NCT00496860). Twenty-six patients with various metastatic, refractory malignancies were enrolled and infused with at least one dose of ALT-801. The clinical data indicated that ALT-801 is well tolerated at the maximum tolerated dose level and exhibits clinical benefit to cancer patients with various advanced diseases with 40% of the patients having disease containment, several with tumor shrinkage and one complete response. This trial was partially supported by an Orphan Products Development Grant from the US FDA.

A multi-center Phase Ib/II trial (Clinical Trials.gov Identifier: NCT01029873) using ALT-801 in combination with cisplatin in patients with metastatic melanoma has been completed. The anti-tumor activity of ALT-801 assessed by the clinical benefit rate is high. The 6-month and 12-month survival are favorable compared with the newly approved drugs vemurafenib (Zelboraf) (Chapman, et al. 2011 N Engl J Med 364:2507 - Pubmed Link) and ipilimumab (Yervoy; anti-CTLA4 mAb) (Robert, et al. 2011 N Engl J Med 364:2517 - Pubmed Link). Another multi-center Phase Ib/II trial (Clinical Trials.gov Identifier: NCT01326871) using ALT-801 in combination with cisplatin and gemcitabine is being conducted in patients with locally advanced or metastatic urothelial carcinomas of the bladder, ureter, renal pelvis and urethra. A very high objective response rate has been observed among enrolled patients regardless whether the patients were chemo-naïve or chemo-experienced. A third multi-center Phase Ib/II trial for ALT-801 in combination with gemcitabine is underway in patients with non-muscle invasive bladder cancer after failing Bacillus Calmette-Guérin (BCG) treatment (Clinical Trials.gov Identifier: NCT01625260). This study is partially supported by a grant from the Florida Department of Health’s James and Esther King Biomedical Research Program awarded to our clinical investigator, Dr. C. J. Rosser of the University of Hawaii Cancer Center.

These Phase II clinical trials for metastatic melanoma, non-muscle invasive bladder cancer, and locally advanced and metastatic bladder cancer are financially supported by a $3 MM NCI-SBIR Bridge Grant awarded to Altor in September 2009.

ALT-801 Fact Sheet (PDF)...

ALT-836 (a recombinant chimeric anti-tissue factor antibody)

In February 2008, Altor entered into a license agreement with Genentech, Inc. for exclusive, worldwide rights to develop and commercialize a class of antibody-based Tissue Factor (“TF”) antagonists.

Inflammation: TF is a membrane protein that initiates the extrinsic coagulation pathway. There is abundant published evidence demonstrating crosstalk between coagulation and inflammation. Coagulation factors activate pro-inflammatory cells and elicit inflammatory responses, while pro-inflammatory cytokines induce TF expression that leads to activation of coagulation factors. In numerous research studies, TF antagonists, including ALT-836, were shown to effectively block coagulation and systemic inflammation. These results provided the foundation for Altor to explore the therapeutic potential of ALT-836in this field, ultimately leading to a Phase I/IIa clinical trial designed to evaluate ALT-836 in patients diagnosed with infection-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two forms of life-threatening, systemic inflammatory disease with a 40% morality rate. Infection-induced ALI/ARDS represents a major unmet medical need and provides an enormous market opportunity for any licensed therapeutic. The Phase I/IIa study was completed in 2006. The results indicated that ALT-836 exhibits biological activities at a well-tolerated level in this patient population (Morris, et al. 2012 BMC Pulm Med 12:5 - Pubmed Link).

In 2009, Altor initiated a multi-center, randomized, placebo-controlled Phase II clinical trial of ALT-836 in ALI/ARDS patients (Clinical Trials.gov Identifier: NCT00879606). Sixty patients enrolled and analysis indicates favorable safety and clinical benefits to patients receiving a single-dose of ALT-836.

A second Phase II, 90-patient trial using a multi-dose regimen to further evaluate safety and efficacy of ALT-836 has been completed. A $3 MM Phase II SBIR competing renewal grant was awarded to Altor by the NIH/NHLBI in May 2011 to support this multi-dose trial.

Cancer: TF is over-expressed by all types of cancers and plays pivotal roles in tumor growth, tumor metastasis and tumor angiogenesis. Clinical studies indicate that the amount of TF expressed by cancers is directly related to metastasis rates and indirectly related to survival. In addition, patients with cancer experience a significantly higher than expected incidence of venous thrombo-embolic disorders, commonly referred to as Trousseau’s syndrome. These complications can be particularly life threatening during chemotherapy and are caused by TF expressed by cancer cells. Inhibition of TF has been shown to reduce tumor growth, metastasis and tumor-induced venous thrombo-embolic events in numerous animal models and represent a novel approach to anticancer therapy.

A Phase I/IIa clinical trial (Clinical Trials.gov Identifier: NCT01325558) to assess safety and antitumor activities of ALT-836 in combination with gemcitabine for locally advanced or metastatic solid tumors failing the standard of care treatment has been concluded. Preliminary results indicate that the treatment regimen provides substantial clinical benefits, including objective responses, to patients with certain cancers.

ALT-836 Fact Sheet (PDF)...

ALT-803 (IL-15 Superagonist Complex)

Altor is also at the forefront of Interleukin-15 (IL-15) based immunotherapeutic technology. The National Cancer Institute (NCI) listed IL-15 as one of the top immunotherapeutic drugs that could potentially cure cancer. As a leading developer of an IL-15-based platform, Altor has created the proprietary IL-15 superagonist complex, ALT-803, with increased ability to bind IL-2Rβγ and enhanced immunostimulatory activity compared to IL-15. Due to encouraging preclinical efficacy and safety results of ALT-803 in animal models, Altor has given ALT-803 a high priority for clinical development and has successfully manufactured clinical ALT-803 material to support the initial phase of multiple clinical trials.

Altor chose to focus the first Phase I/II clinical trial on metastatic melanoma based upon a solid foundation in this disease for various immunotherapies in preclinical and clinical settings. A Phase I/II trial is currently underway to evaluate ALT-803 in patients with metastatic melanoma. Altor and the lead investigator of this trial have been awarded a grant from the Melanoma Research Alliance to support this study. Patients have been enrolled at initial dose levels in this trial. The second study is a multi-center, Phase I/II clinical trial for patients who have relapsed more than 60 days after allogeneic stem cell transplantation for a hematologic malignancy. Multiple patients have been enrolled in this trial at the initial dose level. This trial is partially funded by grants from National Institutes of Health/National Cancer Institute. The third trial is a multi-center, Phase I/II clinical trial for patient with BCG-naïve non-muscle invasive bladder cancer in combination with BCG. Patient enrollment for trial has also been initiated. The fourth study is a multi-center, Phase I/II clinical trial for patients with refractory multiple myeloma. The non-muscle invasive bladder cancer and refractory multiple myeloma studies are supported by grants awarded to Altor by NCI through the SBIR mechanism.

ALT-803 Fact Sheet (PDF)...

Product Development

First-in-class product candidates derived from the STAR™, Tissue Factor Antagonists and IL-15 Platforms are currently in various stages of clinical trials. This strong product pipeline is further reinforced by the numerous other product candidates that have completed proof-of-principle studies in animal models and are at the preclinical development stage.

STAR™ Agents for Cancer

ALT-802: In addition to the clinical development of ALT-801, Altor is advancing its second STAR™ cancer product, ALT-802, a fusion of the p53-specific scTCR to the heavy chain constant domain of human IgG1, providing the Fc domain to invoke ADCC against p53+ cancer cells. In mouse xenograft models, this product shows good efficacy against NSCLC and synergistic anti-tumor activity when used in combination with cisplatin, the first-line, standard-of-care treatment for NSCLC.

ALT-802 Fact Sheet (PDF)...

ALT-804: This is a fusion of the p53-specific scTCR to the IL-15 super-agonist mutein complexed with IL-15Ra-Fc and is undergoing pre-clinical studies.

Cancer Therapeutics – other (non-p53) targeted agents: Altor has several additional non-p53 scTCRs targeting tumor-associated antigens, including MAGE A3, gp100 and MART-1. The scTCRs have been generated, enhanced for affinity, configured into various formats and have entered pre-clinical evaluation.

STAR™ Fusion Agents for Viral Infections

Altor is developing a large portfolio of human-derived STAR™ molecules against viral antigens from HIV, hepatitis C (HCV), and cytomegalovirus (CMV). These STAR™ molecules are being engineered into various formats as fusion proteins and drug or radioisotope conjugates to deliver viral therapies to diseased tissues. The Company intends to continue preclinical development of these STAR™ molecules and seek partnership opportunities for these and other targets.

Altor Antiviral TCR Platform (PDF)...

STAR™ Multimers Reagents

Altor has launched an exciting new class of innovative products based on its proprietary STAR™ technology. These products enable the detection of novel disease targets presented on the surface of cells and tissues. Altor continues to expand the reagent product portfolio.

Research Reagents...

Literature and Publications...