Prolong Expands Operations (& Potential for Success) / by Scott A.

Advanced manufacturing strategy supports long-term business goals

Prolong Pharmaceuticals LLC recently announced the expansion of its South Plainfield, New Jersey, biologics processing facility, adding 24,000 square feet in a move that essentially doubles its original manufacturing capacity to 48,000 square feet. Originally established in 2005 as a research lab, Prolong is led by a team of veteran pharmaceutical executives who are hard at work developing an emerging portfolio of hematology and oncology products to treat anemias, cancers and the debilitating comorbidities associated with these conditions.

With an additional 24,000 sq. ft of manufacturing space, Prolong Pharmaceuticals is pushing its operational strategy forward, an imperative made necessary by the pending regulatory approval of SANGUINATE, the company’s new sickle-cell anemia therapy.

Prolong’s leadership characterizes itself as a mature, privately held biotech company, but virtually anyone who is aware of the company would likely say that’s an understatement. With multiple clinical development programs underway, Prolong currently fields large-scale cGMP manufacturing at its South Plainfield site. According to the company, its operations have been used since early 2010 to produce (at clinical scale) the company’s biological oxygen transfer agent, SANGUINATE. Its recent addition of manufacturing space is part of its long-term strategy to meet the likely commercial success and potential demand for its highly promising sickle-cell-anemia therapy.

In October 2013, Prolong presented Phase I data for SANGUINATE, its intravenous therapeutic that combines the beneficial functions of a carbon monoxide releasing molecule with an oxygen transfer agent that acts as a plasma expander. In trials, SANGUINATE was found to be well tolerated, and is now moving forward into several Phase II trials to treat various comorbidities of Sickle Cell disease including those who suffer from painful vaso-occlusive crises.

Also in clinical development is EPEG, a long-acting third generation biologic for the treatment of anemia, a comorbidity common with chronic kidney disease and cancer chemotherapy. Phase I trials are completed, and Prolong retains development and commercialization rights in the U.S., Europe and China. According to the company, Zydus-Cadila has rights to it in the rest of the world. Also on deck is ANF-Rho, the result of combining state-of-the-art protein engineering technology with advanced PEGylation techniques to create a novel molecule with a unique mechanism of action.  Phase I trials began in 4Q/2014. Also in the pipeline is PP-403, a novel cytokine with broad applications in cancer.In Prolong’s press release announcing the expansion, its president, Glenn Kazo, explained, “As our clinical plans have advanced, we are executing our facilities plan as well. We secured our initial plant with a long-term lease in 2011, and we brought in an industry veteran as vice president of manufacturing and facilities, Tom Flachmeyer. This expansion and the establishment of our new separate corporate offices is on pace with our strategic schedule.”

Prolong says the expansion marks the beginning of an exciting new phase for the company and that along with doubling its manufacturing and administrative space, they expect their workforce to grow by approximately 30 percent during 2015. According to Prolong, the new manufacturing facility should be completed by the second quarter of 2015. “We are moving with this construction with our full efforts,” said Dr. Abraham Abuchowski, Prolong’s chief scientific officer and CEO, “and this will be one of the most unique and advanced large-scale biological product manufacturing facilities in the world.”

Explaining the timing of the expansion, Kazo notes, “The obvious reason is that we’re in Phase II trials after a very successful Phase I trial. Given that it’s a biological product, we have to prepare for Phase III well in advance of the start of the trial.” Kazo explains that like for any drug maker moving new therapy through its regulatory paces, one has to start the process of developing manufacturing in a compliant way so that the commercial facility, not to mention the actual process, is at least validated and ready to go upon FDA approval.

“We are going through that right now,” says Kazo, “and from a timeline point of view, it’s relevant that we begin to process now.” Kazo says Prolong’s facility is unique in a number of respects. For one, he explains, the company has been processing polyethylene glycol (PEG) in large volumes for a number of years, a primary material used in the manufacturing of SANGUINATE. “The really interesting dynamic is that we are producing a large-volume product as opposed to the typical biotech product, which is usually a very small-volume injectable.” To put the scale in perspective, Prolong measures things by loads of metric tons, not by milligrams, which turns on its head the usual scale of biologics production — something that characterizes (ultimately) the commercial (and clinical) processing of SANGUINATE.

“I think SANGUINATE has the potential to be a major medical breakthrough, able to deliver great therapeutic benefit and treat a large number of conditions,” says Kazo. “Although we’re currently seeking approval for one or two applications, I think the total number of applications for the product will ultimately be enormous, which may place manufacturing capacity constraints on us.” Kazo explains the product is effective at treating ischemia or anemia, regardless of the etiology of the disease, such as cardiovascular indications including myocardial infarction, stroke and diabetic leg ulcers, says Kazo.

As mentioned, Prolong brought in an industry vet to lead manufacturing operations. Flachmeyer says that from the moment he saw the product profile, he wanted to lead operations, expressing what motivates and satisfies many in the pharmaceutical industry: “You know it’s very few times in your life when you can get involved in something that’s going to make a difference to humanity.”

He explains that to create commercial scale operations for SANGUINATE the process needs to be sequential and oriented spatially to optimize process steps and keep it within an economically manageable footprint. “One could do one string of pearls a week and then go to the second string, but that’s not a process that’s going to be commercializeable. It has to be sequential and efficient,” says Flachmeyer. Staging raw materials is part of this tactical approach. Flachmeyer says Prolong is going to do something that not many companies have tried with an unprecedented process scale. “We’re not doing this in liters, or hundreds of liters, we’re doing mixing in metric-ton quantities. Now that’s unprecedented.”

“We are building a unique process to streamline every facet of our manufacturing operations, including a fully automated electronic batch process that provides consistency in manufacturing at the volumes we require,” Flachmeyer says. Prolong is taking advantage of some of the most sophisticated technology available, as well as single-use systems and fitting the high-volume process into the smallest footprint they can. “That was our goal. The first manufacturing train is really a scale-up platform that increases our production capacity by about ten-fold and sets the design for future expansion,” he says, with the idea being that Prolong’s facility will be able to produce commercial product with sufficient capacity to meet demand for the first approved indications and then be repeatable to meet anticipated demand growth as further indications are approved by regulators. The growth strategy gives us flexibility to say, “Okay, before we start building multi-million dollar facilities in number, we want to learn a few things but still have a commercializeable process at scale to meet demand. So we want to have enough flexibility to do multi-train and/or multi-product production. It’s designed to be a multi-use facility capable of also producing clinical materials for our other pipeline products.”

Prolong leadership agrees that that such flexibility is not only by necessity but it’s money well spent to create a technology platform that will ultimately allow the company to reach its business goals but create a production environment that not only serves Prolong’s needs right now, but also helps it control costs, manage compliance and other risk elements for the long, long term.