Looking to move more strongly into the emerging field of cancer immunotherapies, Novartis AG announced a collaboration with the University of Pennsylvania on Aug. 6 under which a joint team of researchers will work to discover and develop anti-cancer immunotherapies that target chimeric antigen receptors (CAR). Novartis gains worldwide rights to CART-19, a Penn-discovered anti-CD19 candidate that is being tested in a pilot clinical trial in chronic lymphocytic leukemia.

No deal terms were disclosed; Novartis said it will pay Penn an upfront payment, research funding, milestones pegged to clinical, regulatory and commercial achievements and royalties on any products that reach the market. In addition, Novartis will establish an R&D facility – the Center for Advanced Cellular Therapies – where the work will take place on the university’s Philadelphia campus. Mark Fishman, president of the Novartis Institutes for BioMedical Research, confirmed in an interview that the company will commit $20 million to pay for the R&D site.

The deal grants Novartis worldwide license to all CAR compounds developed through the partnership, but the primary focus at the start is CART-19. Discovered at Penn by a team led by Carl June, director of translational research at the university’s Abramson Cancer Center and Perelman School of Medicine, CART-19 has yielded headline-making results in a three-patient pilot trial in CLL.

The drug showed potent anti-leukemic effects in CLL patients who previously had undergone multiple courses of chemotherapy and biological therapy. Two of the patients were in remission more than one year after beginning therapy with the candidate, while a third has maintained partial remission for seven months. Novartis plans to begin a Phase II trial with CART-19 during the fourth quarter of 2012.

While Novartis is taking a gamble on CAR therapeutics based on data from just three patients, Fishman emphasized the quality of the data.

“There’s no question this is an investigational drug,” he said. “This was quite dramatic a result in those three patients, who formerly would have been hopeless. I think there’s some value in more numbers … but the effects lasted quite a long time, so it wasn’t a short-term remission in at least two of the three patients and the other one is doing quite well too.”

Candidate May Be Effective In Other CD19-Expressing Cancers

Details are still being worked out for the impending Phase II trial, so Fishman could not provide information on how many patients would be tested or for how long of a treatment regime. But the early goal will be to learn how the candidate performs in a larger sample size and if its effects extend to other types of cancer.

“We have to first make sure that this works in a larger number of patients or understand the subgroup in which it does,” he explained. “If it works in patients with CLL, then as a next step we could go into other CD19-expressing tumors, such as B-cell acute lymphocytic leukemia or diffuse large B-cell lymphoma. And there are others that express this particular antigen.”

Like Dendreon Corp.’s prostate cancer drug Provenge (sipuleucel-T), CART-19 and the other CAR therapeutics Novartis and Penn will seek to develop will be personalized therapies derived from extracting and transforming a patient’s own cells. In the case of CAR therapeutics, immune T cells are drawn from the patient’s blood and then re-coded to identify and seek out cells expressing proteins present on the cancer cells in the patient’s body. In theory, when the re-coded T cells are injected back into the patient’s bloodstream, they bind to and destroy targeted cancer cells.

Provenge made a landmark entry as the first immunotherapy approved for cancer when it was approved in April 2010, but it has had a tumultuous go as a commercial drug. On July 30, Dendreon again announced Provenge sales would not meet projections, and the company announced plans cut 600 jobs and close one of three manufacturing sites Also see "As Provenge Sales Dip, Dendreon Hopes Restructuring Is The Answer" - Pink Sheet, 31 July, 2012..

Penn’s technology uses a de-activated form of HIV-1 virus as a delivery agent for its drug. Fishman said June’s lab has been working with that virus for a number of years over a variety of diseases and understands the mechanism well.

“They’ve found it to be quite safe,” he said. “It’s small, it’s easy to work with, we know how to cripple it and it’s been now in the clinic in a reasonable number of patients for a fairly long period of time and that gives us some comfort with it.”

Asked about Novartis partnering strategy when it comes to academia versus biotechs, Fishman said Novartis is simply partnering where scientific opportunities can be found.

“We’ve been very enthusiastic about both [types of partners],” he said. “It’s simply a matter of the opportunities that come along. We have many different types of academic relationships that range from these fairly large formal ones to hundreds of smaller scientist-to-scientist ones. There hasn’t been a conscious decision to do anything than work with outstanding scientists.”

In a prior cancer immunotherapy-related transaction, Novartis in 2010 signed an option deal with Transgene SA around TG4010, an experimental vaccine in Phase IIb/III study for MUCI-positive non-small cell lung cancer. Novartis will pay a $10 million fee if it elects to license the candidate after data from that trial come in. The deal also calls for up to $956 million in potential milestones and royalties [See Deal].

Novartis/Penn To Research Chimeric Antigen Receptor Immunotherapies

More from United States

More from North America