Enzon Pharmaceuticals: A Two-Platform Company

| About: Enzon Pharmaceuticals, (ENZN)

Enzon Pharmaceuticals (NASDAQ:ENZN) is a developmental stage company with a product in Phase II and two in Phase I. The biotech’s pipeline is powered by two platform technologies- Customized-linker enhanced PEGylation, and Locked Nucleic Acid (LNA) antisense. I had a chance to speak with the company’s Chief Scientific Officer, Dr. Ivan Horak last week to discuss their drug pipeline.

The lead compound in Enzon’s pipeline is PEG-SN38, a PEGylated form of SN-38, the active metabolite of the chemotherapy, Camptosar. SN-38 is up to 1000 times more potent than its parent compound, but due to solubility problems, cannot be delivered on its own. Considerable research is being conducted to devise a workable solution, usually involving new formulations such as lipid encapsulation.

The solution Enzon came up with is the attachment of polyethylene glycol (PEG) using a special linker to enhance solubility, reduce toxicity, and increase stability. Dr. Horak believes the resulting compound they are developing is safer than that of other drug makers. In phase I dose limiting toxicity is short-lived neutropenia.

Dr. Horak suggests PEGylation of SN-38 has resulted in additional mechanisms of action not seen to the same extent in the un-altered compound. SN-38 is known as a potent topoisomerase I inhibitor. PEG-SN38 in addition to effectively inhibiting topoisomerase I, inhibits HIF-1α, a possibly oncogenic protein upregulated in tumors. HIF-1 α controls genes involved in cell proliferation, survival, and angiogenesis. This behavior, Dr. Horak explains, makes PEG-SN38 more of a novel molecule than a new formulation.

The compound is now in a Phase II trials in 3rd line colorectal cancer and metastatic breast cancer. The colorectal trial will enroll a total of 220 patients, divided into 2 groups: in one group, patients with tumors with mutated KRAS receive PEG-SN38 as single agent; in the second group, KRAS wild-type tumors, patients are randomized 2:1 to either PEG-SN38 plus Erbitux (arm B), or Camtosar plus Erbitux (arm C). The metastatic breast cancer trial will enroll 160 patients in a single agent study.

Enzon’s second platform is a third generation antisense technology called Locked Nucleic Acid (LNA), licensed from Santaris Pharma. According to Dr. Horak, LNA is a significant technological improvement over the previous generation, providing higher affinity, stability, and selectivity- so much so that the size of these new antisense molecules can be reduced from 20-22 bases (mers), down to between 10-15 mers (preferably >12 mers) while maintaining similar potency. Dr. Horak added that another benefit of these new molecules is lower immunoactivation compared older antisense molecules.

Aside from its lead compound, the rest of the company’s pipeline is built on LNA antisense. This includes EZN-2968, a molecule targeting HIF-1α and EZN-3042, which targets survivin. Both of these are in Phase I. A pre-clinical candidate targeting the androgen receptor is close to entering clinical trials.

Dr. Horak noted the NCI is working in collaboration with Enzon to test PEG-SN38 in combination with Avastin in a Phase I trial under the theory that suppression of HIF-1α by PEG-SN38 will disrupt an escape hatch used by tumors when treated with the anti-angiogenesis drug Avastin.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

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