VentureBeat

(UPDATED: See below.)
Is there a better way to combine drugs in cancer chemotherapy? Celator Pharmaceuticals, a Princeton, N.J., venture drug maker that just raised $10 million, aims to find out.

Like Horizon Therapeutics, which we wrote about here, Celator is convinced that combining two existing drugs in a single formulation at the right proportions can yield better results than current treatments. Although many chemo drugs are already used in combination, the drugs that can be used this way are limited by their side effects. For instance, two chemo drugs that cause severe nausea can’t be used together, because each would have to be given at a less-than-optimal dose in order not to completely debilitate the patient.

In addition, Celator is convinced that various chemo drugs — and here we’re talking about traditional “cytotoxic” chemotherapy that typically kills off all cells that divide quickly, including those that line hair follicles or the digestive tract — tend to work either in concert or at odds depending on the balance in which they’re delivered. So by identifying the drugs that work best together when mixed at an optimum ratio, the company hopes to enhance chemo’s tumor-killing power while minimizing side effects.

Sounds great. Does it work? So far, it’s hard to say. Celator’s lead candidate, CPX-1, is a combination of irinotecan and floxuridine at the cleverly derived molar ratio of, um, one to one. That drug is now in mid-stage human trials. The company’s second candidate, a combination of cytarabine and daunorubicin known as CPX-351, is entering a phase I trial against acute myeloid leukemia.

There are a few cautionary notes. In an earlier “phase I” test of CPX-1 in 26 patients, 15 saw their tumors stabilize for at least two months and two experienced tumor shrinkage (see the PDF “poster” on the study here). Of course, like most early-stage trials, that test wasn’t randomized, controlled or blinded — every patient got the drug — which pretty strongly limits the conclusions you can reasonably draw from it. It certainly doesn’t support the company’s claim in its press release that “over 70 percent of cancer patients in the trial showed a clinical benefit.” For the record, 17/26 is 65 percent, not 70 percent; you can only get to the 70 percent figure by ignoring the data for three patients whose cancer wasn’t “evaluated,” including one who lived less than two weeks after getting the drug. It’s also kind of dicey to claim “clinical benefit” for a drug when you can’t answer the question, “Compared to what?” — which this trial most certainly wasn’t designed to address.

Still, it’s early days for this sort of combination-drug work, and Celator’s investors certainly seem game to tag along. Investors in this follow-on to the company’s $40 million second funding in 2005 included Domain Associates, Quaker BioVentures, TL Ventures, Ventures West Management, GrowthWorks Capital, the Business Development Bank of Canada, and Hearthstone Investment.

The New Jersey Star-Ledger has more here.

UPDATED: Added some additional thoughts on Celator’s claim of “clinical benefit” in its phase I trial.

UPDATE REDUX: Celator’s PR rep lodged a factual objection to the original lead sentence, so I’ve tweaked it.

Palo Alto, Calif.-based Horizon Therapeutics, a biotech that aims to combine existing generic drugs to fight pain, raised $30 million in a third funding round. The company’s lead drug candidate, known only as HZT-501, is a “proprietary” combination of the generic drugs ibuprofen and famotidine, the latter of which is better known by its brand name Pepcid. It’s aimed at providing pain relief without gastrointestinal discomfort or injury, which is the same claim made by Cox-2 inhibitors such as Merck’s withdrawn pain drug Vioxx.

Horizon’s basic idea, which is both interesting and risky, is that packaging together existing drugs like these into a single pill may ameliorate side effects. Famotidine, for instance, suppresses the production of stomach acid, so by combining it with ibuprofen, Horizon hopes to reduce the likelihood of ibuprofen-related ulcers.

That’s the interesting part. The risky part is that patients and their doctors can usually just take the existing generic drugs together for the the same effect. Horizon hopes that its combination pill will prove more convenient for patients than the separate drugs. Would-be competitors to HZT-501, for instance, have different dosing schedules — two to three times a day for ibuprofen, but only once or twice a day for famotidine. (Hat tip to Lou Bock, a VC at Scale Venture Partners, who described Horizon’s strategy in the course of a longer conversation nearly two weeks ago.)

Will that be enough for Horizon to fend off generic competition? It’s hard to say, but Horizon’s backers clearly want to believe it will be. The latest round was led by Essex Woodlands Health Ventures, who was joined by existing investors Scale Venture Partners, Sutter Hill Ventures and Pequot Ventures.

Horizon has previously raised $21 million in equity funding. The company said the latest round will allow it to push HZT-501 through its current late-stage trials and potentially into an approval filing with the FDA, while also advancing a second drug candidate, HZT-602, into late-stage trials. HZT-602 combines another painkiller, naproxen, with famotidine. Naproxen is better known by its over-the-counter name Aleve.