Combination Therapies. Inhibitors

Transcription

1 Combination Therapies with Immune The Value of Partnerships Checkpoint - Case Study - Inhibitors The Value of Partnerships - Case Study -

2 New data is forecasting that the immune checkpoint inhibitor market is primed to become a multi-billion dollar market over the next 10 years. Recent research has identified that a main contributor to the market s bright potential is the level of clinical trial collaborations that have been evaluating immune checkpoint inhibitors in line with combination therapies. [2] Around 40 collaborations are said to have occurred between January 2014 to May With the market s trajectory in mind, Pharma IQ chats to Grant Risdon, PhD, Head of Corporate Development at AgonOx, a biotechnology company focused on cancer immunotherapy. Combination Therapies with Immune Checkpoint Inhibitors Case Study So how will collaborations in regards to combination therapies benefit the immune checkpoint inhibitor (ICI) market? We expect to see an increase in collaborations seeking to identify effective new combinations of approved ICI s with novel agents. Such collaborations should benefit 2 patients by accelerating the development of new treatment options. This interest in identifying optimal ICI combinations will also impact licensing deals. Some will pursue exclusivity, but as companies work to identify the best approved ICI to pair with their novel checkpoint molecules, we expect to see

3 an increase in indication-specific licenses. In other words, we expect to see deals and relationships that take advantage of the fact that one company has an ICI approved in a disease setting where another does not. For the leading company, developing new combinations represents an opportunity to solidify their market position. For the trailing companies, the evaluation of new combinations could represent an approval path not otherwise available to them. It s going to be an exciting era as companies seek to speed the development of new treatments for patients. What is the most interesting ICI combination therapy that you ve seen or heard in the industry s pipeline? That s a tough one as we learn about another combination on a daily basis. I will admit to some bias, we are working on OX40-based therapies in partnership with Medimmune and we think there s a great deal of potential for OX40 agonists in combination with checkpoint inhibition targeted at both CTLA4 and PD-1 pathways. Therapeutics directed at targets that are not traditional T-cell targets will be extremely interesting. Targets such as cytokines elicited from tumor-associated macrophages represent another level of immune regulation entering combination studies. Beyond the current focus on Tregs and cytotoxic T-cells, we are beginning to appreciate that tumor microenvironment interactions involving subsets of B-cells, antigenpresenting cells, and the stroma represent potential targets. In my thinking, those represent the next wave of therapeutic targets for immuno-oncology. 3

4 Pharma The IQ Value and Cold of Partnerships Chain IQ: Top - Case Content Study For Give us an overview of your personal experience with combination therapies within ICIs and the challenges you encountered Our experience at AgonOx is directly related to our clinical-stage OX40 agonists. to be market leaders in terms of ICI combination therapy? Today Merck and BMS are market leaders in ICI but no one should discount Medimmune or others seeking to enter the field. Preclinical studies confirm we have an agent which is active in combination with other ICIs. But less clear, is which combinations will be effective in cancer patients. In partnership with Medimmune the clinical development of OX40 agonists is a balance of combinations and tumor types. Since oncology drugs are approved for specific indications, the challenge for clinical development is similar for all companies; identify the shortest route to approval in a rapidly changing marketplace. Agonox is fortunate to have an experienced and motivated partner in Medimmune. Who would you say are shaping up 4 We can also start to think of market leaders in specific indications where a company has an approved drug that might have improved efficacy when used with an ICI. Take hematologic malignancies as an example. We are seeing companies like Celgene and Seattle Genetics initiate studies with PD1 pathway inhibitors and their approved agents. Success in those studies will further expand their place in the market. I think what s really exciting for me as an immunologist is to see the start of a shift from traditional oncology drugs to immune-targeted therapies. The shift within oncology-companies that sell a multitude of chemotherapies and other agents towards an appreciation

5 that immune modulation will indeed be a major component of cancer therapy seems unprecedented. It s hard for people to imagine but this is something that we ve talked about for 20-plus years. This is always a hope but there s been, as you know, so many failures along the way. Now we re in a situation where something like melanoma, that was pretty much incurable, has now got, a couple different therapies that can have a huge impact and that didn t exist even five years ago. So, I think that s great. It s going to benefit patients with a better safety profile and hopefully a better, longterm outcome as well and it s a pretty interesting time. What are the challenges encountered when developing partnerships with a view for combination therapies for ICIs? I think the challenges are, not surprisingly related to converting a preclinical data into a clinical development program. While the animal model systems provide us with great insights, their limitations are signficant. Another challenge is the paucity of good biomarkers for activity in clinical trials. In the absence of validated biomarkers, we rely on tumor measurements. But tumor shrinkage won t necessarily confirm that a given combination of A followed by B is providing us with changes in immune activity that might provide patient benefit. In the absence of predictive biomarkers, we struggle to understand the best approach and rely on empirical data. Otherwise, how does one determine if B should be given before A or the optimal dose schedule of those agents.. As you know, in many of these situations the immune response requires that the tumour infiltrate expand before the tumor shirinks. As a result it can take a long time from that initial treatment to observe patient response or benefit. So, I think those are going to be some of the big complications. And people who are successful at building those kinds of biomarker tools are going to have a 5

6 significant advantage. Then I think the second one is related to understanding all the different combinations and permutations. It gets quite complicated, because trying to understand at what moment for instance to turn on the killer T-cells and turn off the regulatory T-cells will impact the response. It going to be empirical until validated biomarkers are available. This means trials will be complex. Evaluating multiple combinations will be expensive. Industry analysis state that ICIs are expected to account for around 6% of cancer treatments by How many of these do you expect will be combination therapies? I think the field at large believes that the vast majority of those will indeed be combinations, that you need to turn off one aspect and turn on another and the timing of those things that we discussed is critical. But I think we re also going to see combinations with small molecule inhibitors that are either maybe tumourdirected or they may be directed against inflammatory cell components that are targeted by a protein therapy. There are a number of different pathways that could be addressed through small molecule targeting and I think that is going to expand significantly as well. And if for no other reason you might expect it because cost being an ongoing factor, small molecule treatments have a tendency to be a little less expensive and so you might find that that combination is appealing if you can get the clinical benefit without the cost. So, I think we re always looking for the best patient benefit, in spite of what it might cost I think small molecules will start to have a bigger role as well as we try to manage costs with these treatments as best we can. Grant Risdon, Head of Corporate Development at AgonOx, will be present at the 2016 Immune Checkpoint 6

7 Modulation and Combination therapies conference, which aims to provide an exclusive platform that accelerates learning and facilitates networking between a multi-stakeholder audience with the ultimate aim of improve the effectiveness of immune-oncology drug development. Resources home/ /en/research- Markets-Immune-Checkpoint-Inhibitors- Market-- 7

8 12-14 April, 2016 UK This event will provide delegates with an exclusive platform that accelerates learning and facilitates networking between a multi-stakeholder audience with the ultimate aim of improve the effectiveness of immune-oncology drug development. 5 Reasons to Attend Learn about validating predictive and robust biomarkers to monitor the success of your clinical trials Discover novel immune checkpoint pathways beyond PD-1 Devise targeted commercial strategies to ensure the market success of your next product Hear as yet unpublished data on next generation sequencing Listen to immune-oncology experts reveal novel case-studies on their latest research