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  pipeline  
 

In pursuit of our mission, advancing tomorrow's discoveries, Advanced Cancer Therapeutics has obtained exclusive licenses to four (4) novel anti-cancer therapeutics. The pipeline below depicts these products selected from several opportunities discovered by scientists at the James Graham Brown Cancer Center in Louisville.

prioritized anti-cancer product pipeline

 
   
  ACT-GRO-777 (DNA aptamer)

In April 2011, ACT acquired 100% rights to Antisoma’s clinical stage asset, AS1411, now referred to as ACT-GRO-777. ACT-GRO-777 is an aptamer that binds to a protein called nucleolin which is found on the surface of many cancer cells. ACT-GRO-777 binds to nucleolin and causes cancer cell death. Phase I and II human clinical trials have reported evidence of anti-cancer activity and a favorable safety profile. ACT is evaluating ACT-GRO-777 for additional human cancer trials in collaboration with the James Graham Brown Cancer Center.

 

PU27 (Oligo Quadruplex)

PU27 is a synthetic oligonucleotide which is a novel anticancer compound. It represents a naturally occurring, genomic DNA sequence which is present in two copies in every human cell. PU27 has the ability to form four-stranded (quadruplex) DNA and is located in the promoter of the c-myc gene, a gene which is involved in more than 80% of human tumors. We have demonstrated that the addition of exogenous PU27 inhibits the growth of cancer cells but has no effect on nonmalignant cells. PU27 is active against a wide variety of tumor types, including leukemia, prostate cancer, renal cancer and breast cancer cell lines. The growth inhibitory activity of PU27 was discovered because of its ability to bind and inhibit the enzymatic activity of a-enolase, a glycolytic pathway enzyme. Treated cells also demonstrate altered oncogene expression and decreased telomerase activity.

The ability of PU27 to selectively inhibit cancer cell metabolism and cell growth has important implications for its use as an anticancer agent.

 

PFKFB3 (small molecule)

The marked increase in glucose uptake and conversion by cancer cells has been known for many years. It is the biological basis for the most commonly used cancer diagnostic imaging technique, positron emission tomography, used for detection and staging of neoplastic tumors. It is also well documented that several oncogenes are directly associated with the increased glycolytic need of cancer cells (HIF1a, KRas, cMyc, PTENů); this increased glycolytic flux in cancer cells was named the Warburg effect. 6Phosphofructo1Kinase (PFK1) is the enzyme that controls the first irreversible step of glycolysis; its activity is allosterically controlled by fructose2,6biphosphate (F26BP). The cellular concentration of F26BP is, in turn, mainly controlled by PFKFB3, an enzyme overexpressed in leukemias, colon, lung, prostate, ovarian, breast, and pancreas tumors. Results from preclinical studies validated PFKFB3 as a relevant cancer target. ACT licensed from Dr. Chesney, a pioneer in cancer metabolism, an inhibitor of PFKFB3, 3PO, that had compelling properties and effectively inhibited glucose uptake by cancer cells and tumor growth inhibition in xenograft studies. As a result of SAR optimization of the properties of this molecule, ACT identified a clinical candidate, PFK158. Results of IND enabling studies demonstrated that this small molecule was a potent inhibitor of PFKFB3, inhibited tumor growth across many tumor models and was welltolerated, thus warranting investigating the clinical benefits of this compound with a novel mechanism of action. ACT is currently conducting an open label, dose escalation, multicenter Phase I trial in patients with advanced malignancies.


Choline Kinase (small molecule)

Choline metabolism is altered in a wide variety of cancers including, lung, breast, ovarian, brain, and prostate cancers. Choline Kinase, the enzyme responsible for the generation of phosphocholine, is the most important enzyme associated with choline metabolism and cell proliferation and is over expressed in most solid tumors. A small molecule, referred to as CK37, inhibits cell proliferation, choline kinase enzymatic activity, and tumor growth in xenograft studies without signs of toxicity. ACT’s medicinal chemistry group is developing analogs to optimize the biologic and pharmacologic properties of CK37 prior to initiating IND enabling studies.