Product Development

Halsa Pharmaceuticals is developing therapeutics to treat metabolic diseases including obesity, diabetes and cancer cachexia. These therapeutics utilize novel mechanisms of action and possess demonstrated efficacy in animals.

One key therapeutic in development is a prescription drug showing significant promise for the treatment of obesity, diabetes and other metabolic diseases, called ZAG (Zinc-Alpha-2-Glycoprotein), an injectable medicine that is intended to diminish body fat in individuals, helping them achieve a healthier body weight. The basis of the medicine is a patented biological material that occurs naturally in the human body and acts as a pivotal regulator of body fat.

A second therapeutic is for the treatment of cancer cachexia, the profound loss of body mass that accompanies the disease.  Halsa’s program in this area is taking advantage of a class of therapeutics that interfere with the biological pathways that generate cachexia, specifically the (PIFR) Proteolysis-Induction Factor Receptor .

ZAG (Zinc-Alpha-2-Glycoprotein)

Halsa is developing this therapeutic for the treatment of Obesity and Diabetes

ZAG is a recombinant protein (biologic) being developed into a prescription pharmaceutical product which will increase ZAG levels in obese patients to normal levels, and reduce body fat to normal levels.

ZAG is a natural regulator of fat in humans and other animals

• Higher ZAG levels cause fat depletion, lower levels of ZAG allow fat accumulation

• There is strong evidence that this compound causes fat depletion in humans

• ZAG shows Proof-of-concept data in animals

• ZAG utilizes a novel biochemical pathway

• ZAG acts directly on adipose, does not impact food intake, water intake, digestion or activity

• Halsa has exclusive intellectual property rights to the therapeutic

PIFR (Proteolysis Induction Factor Receptor)

For the treatment of cancer-caused protein loss and muscle wasting. It has been demonstrated that tumors release a molecule that signals that muscle break-down occur.

Halsa’s novel therapeutic:

• Blocks this signal, causing muscle to lose mass

• Uses a novel biochemical pathway

• Has proof-of-concept data in animals

• Exclusive intellectual property rights

References

ZAG

Russell S.T., Zimmerman T.P., Domin B.A., Tisdale M.J. (2004). Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein. Biochim Biophys Acta. Feb 27;1636(1):59-68.
Sanders P.M., Tisdale M.J. (2004).Effect of zinc-alpha2-glycoprotein (ZAG) on expression of uncoupling proteins in skeletal muscle and adipose tissue. Cancer Lett. Aug 20;212(1):71-81.
Tisdale M.J., Bing C., Bao Y., Jenkins J., Sanders P., Manieri M., Cinti S. and Trayhum P. (2004). Zinc-α2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc. Natl. Acad. Sci. USA 101, 2500-2505, 2004.
Wigmore, S.J., Todorov, P.T., Barber, M.D., Ross, J.A., Fearon, K.C.H. and Tisdale, M.J. (2000) Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor. Br. J. Surg. 87, 53-58.

PIFR
Russell ST, Siren PM, Siren MJ, Tisdale MJ(2008) Attenuation of skeletal muscle atrophy in cancer cachexia by D: -myo-inositol 1,2,6-triphosphate. Cancer Chemother Pharmacol. Dec 27.
Tisdale MJ(2008) Catabolic mediators of cancer cachexia. Curr Opin Support Palliat Care. Dec;2(4):256-61. Review.
Yano CL, Ventrucci G, Field WN, Tisdale MJ, Gomes-Marcondes MC (2008)Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes.BMC Cancer. Jan 28;8:24.
Deans DA, Wigmore SJ, Gilmour H, Tisdale MJ, Fearon KC, Ross JA. (2008) Reply: Expression of the proteolysis-inducing factor core-peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastrooesophageal malignancy. Br J Cancer. Jan 15;98(1):243.
Eley HL, Skipworth RJ, Deans DA, Fearon KC, Tisdale MJ. (2008)Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients.Br J Cancer. Jan 29;98(2):443-9.
Tisdale MJ (2007)Is there a common mechanism linking muscle wasting in various disease types? Curr Opin Support Palliat Care. Dec;1(4):287-92.
Todorov PT, Wyke SM, Tisdale MJ. (2007) Identification and characterization of a membrane receptor for proteolysis-inducing factor on skeletal muscle. Cancer Res. Dec 1;67(23):11419-27.
Russell ST, Eley H, Tisdale MJ. (2007) Role of reactive oxygen species in protein degradation in murine myotubes induced by proteolysis-inducing factor and angiotensin II. Cell Signal. Aug;19(8):1797-806.
Eley HL, Russell ST, Tisdale MJ. (2007) Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase. Br J Cancer. Apr 23;96(8):1216-22.