Sanofi Oncology pipeline update 2013

pharmaphorum's Hannah Blake catches up with Dr Tal Zaks from Sanofi Oncology to see where the global pharma company's oncology pipeline is heading, the unique partnerships that have helped Sanofi with these developments and how these advancements will ultimately help improve the lives of cancer patients in years to come.

This year's American Society of Clinical Oncology (ASCO) annual meeting was held between May 31st and June 4th in Chicago, Illinois, USA. One pharma company that was particularly excited in the run up to this meeting was Sanofi Oncology, who showcased nearly 30 abstracts demonstrating their portfolio, people and partnerships, all focused on improving the lives of patients impacted by cancer. These abstracts focused on the areas of metastatic colorectal cancer, myelofibrosis and prostate cancer, with the common goal to marry cutting-edge science with meaningful patient benefits to treat unmet medical needs.

To find out more about Sanofi's exciting upcoming oncology pipeline, pharmaphorum's Hannah Blake interviewed Dr Tal Zaks, who is the Vice President and Head of Development for Sanofi Oncology based in Cambridge, Massachusetts in the United States. Dr Zaks is responsible for leading the clinical development of compounds through regulatory registration and in addition, currently serves as an adjunct Associate Professor of Medicine at the University of Pennsylvania.

"For us, I think the number one excitement right now is around the JAK2 inhibitor."

Dr Zaks shares with us how Sanofi has been able to leverage its expertise in research and clinical practice, along with unique partnerships with pharma, patient advocacy groups, academia and biotechs, to bring quality healthcare solutions to patients.

Interview summary

HB: It's a pleasure to speak with you today Dr Zaks. To start, could you tell us a bit about your background and your current role at Sanofi please?

TZ: I'm a medical oncologist with background in research – I'm an MD PhD and I did my original research work at the National Cancer Institute (NCI) in tumour immunotherapy. I did some clinical work and research work at the University of Pennsylvania, where I'm still an adjunct faculty, focusing more on cancer genetics, and really was interested in figuring out how to better develop drugs for patients, which is why I joined the pharmaceutical industry.

I've been with Sanofi for the past three years. I joined as part of a new oncology division headquartered in Cambridge, and over the past three years, we've built a team here, recruiting many people, as well as continuing to leverage the people that we have in France. The team is divided between Cambridge in the US, and in Paris, so as to focus on making sure that the drugs we have in research are being appropriately developed and are able to show the benefit to patients at the end of the day. We've had successful approvals and launches in these past three years for Jevtana (cabazitaxel), and more recently of Zaltrap (aflibercept), and we look forward with the positive results for our JAK2 inhibitor to continue in that vein.

HB: Following ASCO 2013, what recent oncology advances within Sanofi are you most excited about?

TZ: For us, I think the number one excitement right now is around the JAK2 inhibitor. We won't yet be able to share the results at ASCO, so we're targeting a future medical meeting for that. But we have met the primary endpoint, and this is a phase III study that actually tested two doses, and I think the ability to show the improvement to patients in that setting is really exciting for us.

Just to take it back a step to give you the context, JAK2 mutations are frequent in a disease known as myelofibrosis when there is a failure of the bone marrow, because an abnormal proliferation of this cell clone, and so these patients have low blood counts, and have constitutional symptoms, because their spleens are enlarged. The spleen is actually the site in the body where the body tries to make blood when it can't do so in the bone marrow. This programme was started by TargeGen, a small company, and we in-licenced the molecule in 2010. At the time, all we had was phase I results. We put a team together, reviewed the results and looked carefully – it was clear back from phase I that you could have a significant impact on these patients in terms of reducing their spleen sizes. And in discussions with the FDA, in the beginning of 2011, we had an agreement that if we show the appropriate dose and we can clearly demonstrate the benefit to patients, both in terms of their spleen shrinking and in terms of their symptoms, that this could be a path to approval. So for us, the ability to show that benefit to patients in a relatively short time, you're talking three years from the time that we took this over to having positive phase III results and were gearing up to discussions with regulatory authorities, I think for us is very exciting.

HB: What impact do you anticipate these advances will have on oncology patients in the future?

TZ: For the JAK2, I think right now there is one competitor available, but treatment options for these patients are extremely limited. This is a disease where the symptom burden is quite heavy, and when the disease is advanced, the overall survival is also fairly short, roughly two to three years or so. So while we won't be showing an improvement in overall survival, the study wasn't set up to do that, I think the ability to have more options for these patients and improve their symptoms, and potentially down the road actually modify this disease, I think is very exciting. So on JAK2 that's where we're heading.

"The ability to launch drugs that have an improvement in overall survival associated with them is really for me the driver of much of what we do."

I'll also give you a sense of where we are in terms of other molecules in the pipeline. I mentioned Jevtana and Zaltrap previously, so Jevtana is a taxane that is approved for prostate cancer with an improvement in overall survival and Zaltrap is an anti-VEGF-A, anti-VEGF-B and anti-PLGF fusion protein that when added to combination chemotherapy in second line colorectal cancer improved their survival. So these are two drugs that we've recently launched that we see patients' usage increase in the marketplace. The ability to launch drugs that have an improvement in overall survival associated with them is really for me the driver of much of what we do.

HB: As a company, Sanofi Oncology has been involved in many unique partnerships, including those with pharma, co-operative groups, and patient advocacy groups. What does Sanofi look for in a partnership?

TZ: One of the things that has changed for us if we step back is that we've really opened up the company from a cultural perspective. This has allowed us to understand how we work as part of the bigger environment, if you will, of drug development, recognising that there are things that we do and we do fairly well, and there are also other things that other groups in other constituencies do and do well. So finding that right fit of understanding what it is that we bring to the table and what the partner brings to the table, to really accelerate our ability to translate things that are exciting in science into concrete medicines for patients, that's the crux of it.

Let me give you some examples. So I mentioned our ability to really accelerate the development of the JAK2 inhibitor, which was of course done with partnerships with key investigators and opinion leaders. But on a different level, if you look at some of the partnerships we've formed with academic institutions, such as in Cambridge we have a very close relationship with the Dana-Farber Cancer Institute and Massachusetts General Hospital (MGH). Part of the mindset that drives collaborations like these is our ability to communicate with these centers and put our new drugs in front of the right patients from the get go and being able to see a signal of activity early on.

Another example is our partnership with the University of California, San Francisco (UCSF), where we took a molecule, that at the time, its activity was completely untested. The molecule was an antibody against CD38 with potential in multiple myeloma. And so what we've done is actually come to UCSF and said let's do a partnership on this whereby you are our partner in the project team. So this wasn't just an institutional partnership, but a partnership at project team level, where there's a physician, translational medicine people from UCSF who are tied at the hip to the project managers, and the drug experts internally at Sanofi. Together, this team has really been able to leverage the expertise that the clinical folks have at UCSF and the expertise that the drug and biologics people have within Sanofi to accelerate the development and really take this drug to phase I, to start another combination study. We won't have any results to share yet, but I am excited and hopefully at an upcoming medical meeting we'll be able to share some of the results of that. So these examples give you a sense of the partnerships that we have in the academic front.

Now clearly within the environment there is also a lot of excitement and a lot of innovation coming up from biotechs, and we look for those partnerships as well. The JAK2 inhibitor actually came out of a biotech. If you look at the molecules we have in phase II, we have two PI3 kinase inhibitors that we have partnered with Exelixis to develop and also an antibody against HER3 that we're doing in collaboration with Merrimack. This is a very unique partnership, because there again we have a project team that has people of Merrimack and people from Sanofi working together and making decisions together, but ultimately it's the biotech partner who is executing on the early clinical development plan for that one. So we're leveraging again the strength of each partner and our own strength as we realise it to accelerate and do a better job in terms of developing drugs.

"...the partnerships that have been successful have been the ones with innovation capabilities in the biotech sphere..."

This is also applicable to the research arena, for example there was a small company called Ascenta, which came out the University of Michigan, who were trying to find a modulator for P53. Our research teams have been looking for one for many years as well. When it became clear that Ascenta had a potential candidate, but it was early and it wasn't clear if there was a path forward for it, our scientists actually worked with them for about a year before we ever signed a formal deal. This was so we could say look here's what it's got to look like in order for us to be interested in it, in order for this to have a potential for patients. What came out of that was a very exciting molecule that we've partnered with them and today is in phase I led by our team, and of course with collaborators, to try and flesh out that benefit to patients. So it gives you a sense of how we approach partnership and what it is we're looking for.

HB: Which partnerships have been most successful and why do you think this has been?

TZ: I think the partnerships that have been successful have been the ones with innovation capabilities in the biotech sphere, because we've been able to leverage their ability to innovate and our ability to understand what it takes in terms of full development, full chemistry, the strength of a large pharma.

On the clinical development side, I think the successful relationships that I've sided with have been with MGH, UCSF and Merrimack. They have been successful because we have found the clinical investigators in the institutions that have similar mindsets of really understanding and doing the right clinical development from the very start. This is in the sense that if you understand what is it about the patient's cancer that you're trying to target and how your drug fits there, then you can quickly find those right patients to treat.

One final example I'll give you is in an area that's exciting for many companies, which is the sense that to be effective in giving a significant benefit to patients you may need to combine more than one pathway inhibitor, and so we've partnered with Merck Serono. Merck Serono has a very interesting MEK inhibitor and we had a PI3 kinase inhibitor, and so there was great interest to put these together. So here is a partnership with a large pharma where there is a very solid scientific rationale for why combining one of their drugs with one of our drugs would work in pre-clinical models, and then going out to MGH and Dana-Farber, and centres in the Netherlands, where you've got investigators who understand that scientific basis, and can translate this into the right clinical trial.

HB: Finally, where do you see the future for Sanofi and its oncology pipeline heading?

TZ: I think we're at an interesting point if I step back and look at the world of drug development pharmacology. We have to straddle the divide of the expectation from ourselves and clearly from the rest of the world, from patients, payers, governments, that we provide a significant benefit to patients. And clearly we need to raise the bar in terms of the magnitude of benefit we bring. I am very proud that the drugs we have launched have either shown a substantial overall survival improvement or a very clear improvement in patients' well-being, but we need to continue to challenge ourselves to make that increase evermore meaningful.

"...clearly the improvements in the acceleration of discovery in science and what drives different cancers needs to be translated into effective medicines."

On the other hand, we've got this emerging science where clearly the improvements in the acceleration of discovery in science and what drives different cancers needs to be translated into effective medicines. There are a couple of places where I think these two come together nicely and where we are playing a major role. One of them is around the concepts of antibody drug conjugates. Antibodies are a way to target a specific cell. In this case we're obviously looking to target a tumour cell. Sanofi has a legacy understanding in cytotoxics, and so our ability to partner, which goes back quite a few years with ImmunoGen who were a pioneer in the field of antibody drug conjugates, and put their platform and capability together with our capabilities to really come up with new and better antibody drug conjugates that can take chemotherapy and put it where it needs to go, straight into the tumour cell, I think is exciting. We have two molecules in clinical research today; there's one in lymphoma against CD19 as the target, and we have another drug that's targeting solid tumours that's currently in phase I. So I think you will continue to see us put an emphasis on antibody drug conjugates as one place in terms from a mechanistic standpoint where I think we can make a benefit. I've mentioned P53 and there are other similar signalling pathways where I think if one inhibits the right pathway and the right patient there is significant clinical benefit that can be obtained.

I think the final piece where I'm excited is in the area of haematological malignancies. For many years, these malignancies have been at the forefront of research because of the simple fact that the tumour cells are readily accessible. Our understanding of stem cells and lineages in haematological malignancies I think is far advanced of what it is in solid tumours, and so the convergence of the science, understanding the patient characteristics, and then bringing the right therapeutic modalities in this disease has really made an impact. If you look at the progress over the past decade in lymphomas and myelomas, I think it's been substantial, and some of our most promising drugs are also in that sphere. I've mentioned the anti-CD38, which is being developed in myeloma. We also have two drugs which are now in phase II studies, both for aggressive lymphoma, that's the CD19 antibody drug conjugate, and for indolent lymphomas, which is a PI3 kinase inhibitor, the one I referred to from Exelixis. So I think within the haematological malignancy space, our ability to continue to bring substantial improvements to these patients in terms of halting their disease and ultimately changing the course of their disease, and improving their overall survival is really significant. I also, of course, think that for us today, the best manifestation of that is what we're able to show with the JAK2 inhibitor in myelofibrosis.

HB: Thank you very much for your time today, Dr Zaks.

About the interviewee:

Dr Tal Zaks M.D., Ph.D., is VP and Head of Development for Sanofi Oncology in Cambridge, MA, responsible for leading the clinical development of compounds through regulatory registration. In addition, he currently serves as an adjunct Associate Professor of Medicine at the University of Pennsylvania.

Prior to his career at Sanofi, Dr Zaks worked at GlaxoSmithKline in the Genetics Research group, where he built an oncology translational medicine team and led genetics, translational, and clinical research on lapatinib as well as the in-licensing and clinical development of foretinib. He received his MD / PhD degree from the Ben Gurion University in Israel and completed his clinical training in internal medicine at Temple University Hospital, followed by a fellowship in medical oncology at the University of Pennsylvania.

What's next for Sanofi Oncology?