Roche’s Push In Cancer Immunotherapy: An Interview With New Exec Hy Levitsky

“Cancer immunology will play a far greater role than it ever has within the [Roche Pharma Research and Early Development Organization] and we hope there will be synergies we can exploit with other treatment modalities under development at Roche,” Levitsky says.

Roche’s appointment of Johns Hopkins cancer immunotherapy expert Hyam Levitsky to a newly created position is a testament to the growing importance of the therapeutic space, as well as an encouraging sign for experimental vaccine developers.

Levitsky has taken on the new position of Head of Cancer Immunotherapy Experimental Medicine within Roche’s Pharma Research and Early Development Organization (pRED) division, which has sites in the U.S., Europe and Asia. Levitsky is responsible for guiding research and early development programs focused on immunotherapy of cancer and overseeing experimental medicine studies and projects, in collaboration with internal or external partners. He will also maintain an academic research appointment at Johns Hopkins, where he has served as professor of oncology, medicine and urology.

Roche and Genentech Inc. have been leaders in monoclonal antibody engineering, both as a means to directly target tumors and manipulate the host immune response to cancer, Levitsky commented in an interview after his appointment was announced in mid-October. Such expertise has helped propel Roche to the number one position in oncology, with $17 billion in sales for 2010, or a 31% global market share (Also see "Global Oncology Rankings: It’s A Long Way To The Top" - Pink Sheet, 30 May, 2011.).

“Cancer immunology will play a far greater role than it ever has within the pRED organization and we hope there will be synergies we can exploit with other treatment modalities under development at Roche,” Levitsky said.

That future could include development of active cancer immunotherapies, also called cancer vaccines, a key area of Levitsky’s expertise.

At Johns Hopkins, Levitsky’s research focused on immunologic mechanisms of vaccine-induced tumor immunity. Up until the time of his appointment at Roche, he served on the board of directors at brain cancer vaccine developer Agenus Inc. (formerly called Antigenics), and has also been a consultant to Celldex Therapeutics Inc., which has also developed a brain cancer vaccine, among many other companies. Levitsky is also a founding executive committee chair of the Cancer Immunotherapy Consortium, now part of the Cancer Research Institute, a non-profit provider of funding for cancer research.

Levitsky’s own discoveries were developed by Cell Genesys Inc., maker of the GVAX cell-based vaccine for prostate cancer. Along with many other late-stage cancer vaccine flameouts, GVAX failed to make it through Phase III, though the platform on which it was based continues to be tested in academic centers (Also see "Cancer Immunotherapy Sees Setback With Failure Of Cell Genesys’ GVAX" - Pink Sheet, 16 Oct, 2008.). Dendreon Corp.’s Provenge did go on to become the first approved cancer vaccine, but has hit some significant commercial roadblocks (Also see "With Dendreon Humbled, Lessons Learned For Cancer Vaccine Makers" - Pink Sheet, 22 Aug, 2011.).

In the interview, Levitsky explained his new role and his early impressions about where cancer immunotherapy development at Roche is headed.

“The Pink Sheet” DAILY: Can you explain your role in more detail?

Levitsky: My role will be to integrate and solidify the presence within the cancer immunotherapy space. This is an area that Roche has been investing in, particularly using their technologies of monoclonal antibody engineering, not only to directly target tumors but to manipulate the host immune response to cancer. So it is not as if this endeavor is starting with me. But my recruitment is a nice testimony to the recognition Roche has that cancer immunotherapy is here to stay and that there are very large opportunities to be developed.

In addition to taking the position of stewardship of existing strategies I am tasked with building at each site a presence in cancer immunotherapy that currently doesn’t exist. And a big part of the job is to look for opportunities externally. Since I spent my entire career in academia, I have a large number of colleagues and collaborators across the world who are moving the field forward in a significant way, and part of my job will be to reach out to those colleagues … to create partnerships for developing promising immunotherapies.

“The Pink Sheet” DAILY: Will the partnerships be developed on an individual basis, or with a model contract you would use for institutions (Also see "Back To School: Big Pharmas Test New Models For Tapping Academia " - In Vivo, 1 Feb, 2011.)?

Levitsky: The honest answer is both. We are in the midst of working out a template for how this might be done. Part of the appeal to Roche of having this new model be explored is to keep a presence in the academic world and allow those opportunities to come forward more quickly. In that spirit, Johns Hopkins will certainly be one of the early centers we will seek to create partnerships with and we are in midst of negotiating at the moment, but it will not be the only site.

I do see opportunities there that create a win-win for both entities. There really a large number of outstanding programs both in the U.S. and around the world where I think this model will apply.

“The Pink Sheet” DAILY: How might Roche’s current early-stage pipeline change with a greater focus on immunotherapy?

Levitsky: It’s still early days to give you a concrete answer to that. I am looking at existing programs within the immunotherapy space. Those that are farthest along and look like they have promise will continue. I have been given the opportunity to round out the portfolio with new directions that are not yet represented.

“The Pink Sheet” DAILY: Is there a reason you have been drawn in the past to working with companies developing vaccines for brain cancer?

Levitsky: I did have involvement with companies in that target. My clinical training was more in hematologic cancers so there wasn’t any specific training or expertise in that clinical domain that led to that. Nevertheless, I do feel those are interesting targets in [an area] of very high unmet medical need.

“The Pink Sheet” DAILY: Will you be focusing on particular diseases thought to respond best to immunotherapy?

Levitsky: We know from pathology literature that various cancers have a naturally a large infiltration of cells from the immune system, whereas others tend not to. These differences likely reflect distinct subtypes of a given cancer.

For example, one disease frequently thought of as the poster child for immune responsive cancers is melanoma. However, if you look carefully at primary or metastatic lesions in melanoma patients, only about half have a strong immune cell infiltrate within the tumor, while others have very little. Melanomas of the latter type often don’t do well, even with immunotherapies that would otherwise be beneficial to others. The distinction is not so much which cancer types we are going after, but rather what are the particular aspects of a given patient’s cancer that would [make] them be responsive to a particular strategy.

“The Pink Sheet” DAILY: There’s an ongoing debate about personalized versus off-the-shelf vaccines, particularly after the hurdles Provenge has faced in breaking into the market. Can you share your thoughts on that?

Levitsky: Dendreon has both the honor and burden of having been the first across the finish line. We all were very happy to see their early successes, though everyone was holding their breath because it is a complicated particular platform.

I think the devil is in the details. For sure, we would all aspire to an off-the-shelf product that is closer to what people are familiar with in oncology – and vaccinology for that matter – and many of the development and regulatory pathways are far more established in that context.

But at the end of the day, it’s the biology that really will determine what works best. We do know that potent immune responses can be generated to what immunologists refer to as shared antigens, those molecules that are present in cancers of many individuals. And clearly a significant component of our cancer vaccine efforts at Roche is going to be looking at such candidates as shared antigens integrated into a number of different vaccine platforms.

Having said that, I have always been of the opinion that if one shows that something works, there are clever enough engineers out there to figure out how to make it workable. This is particularly relevant to personalized vaccines where it may seem almost an insurmountable task to literally make a therapeutic reagent for each individual. And in some instances, in current configurations that is probably a correct assessment. But the technologies are really moving very fast. And between exome sequencing that can be done on individual tumors and rapid turnaround and identification through bioinformatics-assisted identification of targets, it’s not inconceivable that one could literally go from a tumor biopsy to a personalized vaccine in the timeframe that would be needed and at an expense that would be acceptable to go forward, so I have not closed my mind to that possibility.

“The Pink Sheet” DAILY: Then does it follow that Roche will be pursuing development of personalized vaccines?

Levitsky: I would prefer to say I have not closed my mind to the possibility of personalized immunotherapy, whether that is a truly tailor-made vaccine for each person, or on a simpler level coming up with a set of diagnostics or companion assays that would predict which individuals will most benefit from what component of the immune system we target, that also could be appropriately be considered personalized immunotherapy. So sure, it will be part of the portfolio in some fashion or another.

“The Pink Sheet” DAILY: The quality of evidence behind genetic testing has been drawing scrutiny and criticism. How can that challenge be overcome?

Levitsky: It is a work in progress… We haven’t crossed the finish line. We don’t yet know which measures correspond to a patient that will respond vs. not respond to a particular immunotherapy. But that has to be part of the development plan. Maybe I take it on faith that this will be a productive exercise, but until proven otherwise, that is a logical way to proceed.