Medical Device Daily

David Ringler acknowledges that the bioengineering thing has been hyped, even over-hyped, but he says Theregen (San Francisco) isn't taking that route. Rather, he asserts that the company is using a significantly evidence-based approach for its claims.

Those claims will be tested with the company's Phase I study, just launched, and the first procedure in its first-in-man trial: “a living patch of human cells . . . successfully placed for the first time on a patient's diseased heart.”

A surgical team led by Yale University (New Haven, Connecticut) medical researchers recently performed the procedure at the Veteran's Administration Hospital (West Haven, Connecticut), using Anginera, the company's cell-based cardiovascular patch.

Ringler, head of communications for Theregen, told Medical Device Daily that the trial will include 12 patients, the procedures performed at Yale and the University of Maryland (Baltimore). The next trial will be a “combination of safety and limited efficacy, not a full-blown trial,” followed by additional efficacy studies.

The patch material is based on DermaGraft, the skin-substitute product developed by Advanced Tissue Sciences (ATS), a company that went under in 2004 (MDD, June 21, 2004), with the product now owned and marketed by Smith & Nephew (London).

When previously named Iken, Theregen acquired the licensing rights to Dermagraft, specifically for use in the current cardiovascular strategy.

That strategy is to use the product's ability to produce angiogenesis when placed onto the surface of a damaged heart. The platform is the culturing of human fibroblasts grown on a 3-D bioabsorbable scaffold material to create viable tissue. When applied as an epicardial patch to an ischemic area of the heart, the tissue provides a source of the cytokines and growth factors leading to tissue repair, according to the company.

Ringler emphasizes that the clinical trial path will be that which is required of a pharmaceutical, since Anginera is a biologic material, with the regulatory application made to the Center for Biologics of the FDA.

The Anginera patch is used in conjunction with a coronary artery bypass graft (CABG) procedure, with the graft applied “in areas that surgery is not appropriate – where there are open ischemic areas.”

“Dermagraft,” Ringler says, “was used to stimulate blood vessel formation and tissue repair and wounds. That technology led us to run experiments on the heart in animals. We found compelling evidence of angiogenesis. Certain cells – in our case fibroblast cells – secrete these various proteins and cytokines that appear to help stimulate blood vessel formation. We've done this in several different models and it certainly deserves a chance in this very finicky environment.”

The general endpoint for the company's work is to improve the patient's “quality of life [as] the first and foremost measure,” Ringler says.

He readily acknowledges that there is a certain difficulty in differentiating between the effects of the CABG procedure and the effects of the patch.

As an answer, he says: “We feel that based on our clinical measurements going forward, as we move into efficacy phase, we will be able to measure various parameters such as ejection fraction and wall strength in the left atrium that can hopefully be attributed to increased cardiac performance.”

The company's preclinical work supports its evidenced-based approach. It has carried out a variety of studies in mice. Results of one of the earliest studies in mice was published in an issue of Circulation in 2001 – while still being developed by ATS – and demonstrated an ability to improve the function of damaged heart tissue with no adverse effects (MDD, Nov. 16, 2001). (Gail Naughton, formerly president of ATS, is now head of the Theregen board).

Michael Siani-Rose, president of Theregen, said, “We are very pleased to have reached this important milestone for the company, as we believe we are one of the first regenerative medicine companies based in the San Francisco Bay Area to initiate human clinical studies.”

He added: “It is generally recognized by leading physicians that our patch elicits a profound wound healing response when placed on a topical injury.”

Gary Gentzkow, MD, chief medical officer for Theregen, said, “While the primary focus in this Phase I trial is to demonstrate the safety of Anginera, we hope to demonstrate in this and future trials that Anginera's biologic activity can promote the formation of structurally and functionally significant blood vessels in diseased cardiac tissue.”

He added: “This potential, positive re-modeling effect of Anginera may increase blood flow and therefore improve the function of a patient's diseased heart. If proven safe and effective in future trials, this potential therapy could represent a significant advantage in the treatment of diffuse small vessel disease.”

Ringler notes that the money-raising function in the biologics space is not easy, since there have been periods when “the whole bioengineering euphoria was a bit over-hyped.” But he adds: “That has diminished and out of it has come some very quality rational potential applications.”

“Now,” he says, “it's all about results.”

He notes that announcement of the launch of the Phase I trial of Anginera is a result that is attracting a good deal of interest and will serve to build on the company's previous fund-raising efforts.

The company in January received $1.5 million in equity funding from Sanderling Ventures to support the trial, which received go-ahead from the FDA in 2005, and Guidant (Indianapolis) made an investment in the company – the amount not disclosed – in early February.

Ringler declines detailing the company's current cash position or burn rate but says that the company has “sufficient funds to move forward.”