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Building an Outsourcing Strategy that Evolves with your Biotech

Dr Jakob Dupont shares his CRO selection strategies, when to insource and how to think about the shift from insourcing to outsourcing as your company evolves.

June 17, 2021
Building an Outsourcing Strategy that Evolves with your Biotech

Jakob Dupont, MD, is the EVP, Global Head of R&D at Atara Biotherapeutics.
Can you speak about your experience in the biotech industry?

I’m a medical oncologist and tumor immunologist. I started my career in academics at Memorial Sloan Kettering and I have been in industry for fifteen years now. I started in large biotech with Genentech in 2006. I spent five years at Genentech working in oncology on a program called Avastin for gynecologic and breast cancer indications. I also worked in the early clinical group and spent a year in Switzerland. I did six jobs of increasing responsibility in those five years. I helped get Avastin approved for breast cancer and for ovarian and cervical cancer. I also got to file a number of Investigational New Drug applications for anti-angiogenic drug candidates. The drug approvals in particular really met all of my expectations in terms of helping to change the standard of care for populations of cancer patients.

After those five years, I joined a company called OncoMed as CMO back in 2011. We had a really exciting ride for about five and a half years where we filed a number of INDs and conducted a number of clinical trials for first-in-class, novel therapeutic agents targeting cancer stem cells in immuno-oncology. We did an initial public offering. We also set up some big partnerships with Celgene and had other partnerships with big pharmaceutical companies including GlaxoSmithKline and Bayer as well.

Then I was recruited back to Genentech/Roche where I was the Global Head of Breast Cancer and Gynecologic Cancers for Roche globally. We did about eight regulatory filings in two years and managed to bring a number of important drugs to patients suffering from different types of breast cancer. After a couple of years there, I was recruited to a company called Gossamer Bio in San Diego to work as the CMO and oversee the development and regulatory groups for programs focused on immunology therapeutic approaches for cancer and auto-immune diseases. My passion has been figuring out ways in which to target a patient’s immune response for therapeutic purposes. With Gossamer, for the first time, I bridged beyond oncology into other therapeutic areas such as autoimmune disease including multiple sclerosis (MS), asthma, and ulcerative colitis where the immune system is once again the problem.

I am now the Global Head of R&D for Atara Biotherapeutics. This is the culmination of my scientific and medical journey because what I’m working on at Atara is off-the-shelf cell therapies for patients suffering from cancer and autoimmune diseases. I’m actually back and developing the types of cell therapies that I worked on 15-20 years ago at Memorial Sloan Kettering in my oncology fellowship and my early academic faculty career. It’s incredibly satisfying to reconnect to these therapies that I’ve been passionate about for 20 years. We are now close, at Atara, to bringing, for the first time, a donor-derived, off-the-shelf T-cell therapy to regulatory filing with the FDA and EMA. I also get to work with our team on another program for MS where I’m very interested in bringing immune targeting approaches to diseases beyond oncology. We also have important programs of off the shelf allogeneic CAR-T therapy for cancer indications.

How has your outsourcing strategy changed working with these different companies at different stages?

Large pharmaceutical and small to midsize biotechnology companies have very different strategies to outsource. This has a lot to do with the resources that you have at your disposal. When you’re in a small and scrappy biotech, you think very carefully about which development and which research functions you want to retain and build in-house versus outsourcing. I think a lot of this also depends on the stage of the company. If you’re a preclinical to near-IND company, there are a lot of functions that you don’t necessarily need yet. Things like safety and biostatistics may be things that you don’t bring on in that very early biotech realm. You want to make sure that you at least have medical, regulatory and clinical operations in-house so that you can file your IND and start your early clinical trials.

But if you’re in a company that has more advanced- staged programs in phase II and III then you can certainly think about bringing in safety because that becomes a busier function within a later-stage company and you are also closed to regulatory filings. You can think about bringing in biostatistics because you must design those proof-of-concept phase II studies or build your pivotal study to get regulatory approval. That is when you need great biostatistics.

Another concept is efficiently using resources. It makes sense to me that you would want to outsource safety early on in the development of your programs because you don’t want to build a large safety group in-house and have to pay for a lot of full-time equivalents (FTEs) if you can leverage a contract research organization to do a lot of those things.

“You have to anticipate the next stages of your programs. If you have early phase I data that looks encouraging and you think that you may be on a path to design a pivotal trial, you want to make sure that you bring the expertise to support the writing and conduct of that clinical trial.”

As your company evolves, how do you decide what to outsource and when?

You have to anticipate the next stages of your programs. If you have early phase I data that looks encouraging and you think that you may be on a path to design a pivotal trial, you want to make sure that you bring the expertise to support the writing and conduct of that clinical trial. That may mean that you bring in a great biostatistician to help you write your pivotal study. It may mean that you bring in more senior regulatory expertise to support FDA and EMA conversations. You need to bring in those people that will help you design that next stage of development.

There are a few key functions that I always like to have in-house because they are so central to your success in a biotech company. One of those key functions is clinical development – your physician scientist who will help you write and run those clinical trials. You want to have an in-house regulatory person who you can partner with on your development or IND-filing strategy. Having a great in-house clinical operations hire is also really important because you have to operationalize your clinical trials.

Another thing I’d think about as you get closer to pivotal studies is quality. There is a point at which a biotech gets closer to phase III drug development and pivotal drug development when you really want to make sure that your quality systems are up to snuff for regulatory inspections.

Depending on the type of therapeutic that you’re developing, there are a couple of other functions that can be quite important. Translational science can either sit in the clinical group or the research group or straddle between the two. Having a great partner on the translational side to help you with identifying and building predictive biomarkers and understanding the pharmacodynamic data you’re generating in the clinic is really important. Depending on the type of drug that you have, a great pharmacokinetics (PK) scientist can help you to understand the way to be dosing your drug in the clinic. This can really vary depending on whether you are developing a small molecule, large molecule or cell therapy. That PK scientist you look for needs to be catered to the type of therapy that you’re developing.

What kind of functions do you outsource?

There are a few different principles when outsourcing. You can either hire a CRO with an outsource model or you can hire individual consultants who can bring certain levels of expertise into your company. I use both approaches. Some of the functions I tend to outsource to CROs include safety. I think that it is pretty useful to have an outsourced safety group that you can leverage, especially if you are conducting international clinical trials. You can leverage a group that has a presence in Europe or Australia to provide ready access to your investigators in those places. There is a point at which you bring safety in-house as you get closer to registration and pivotal trials. But early on, it is useful to outsource safety.

Biostatistics can also be outsourced. You have to be careful and make sure that you get very good expertise from a CRO on the biostatistics side because there is a lot of variability. You need to assess the candidates offered on the biostatistics side to make sure that they are good. As you advance more to pivotal trials, I like to make sure that we have in-house biostatistics to help design your pivotal clinical trials as well.

Data management is another function that I tend to use the CRO for. Clinical Operations is another one. Operationalizing the study and making sure that you hire a great CRO to partner with is really important. But, as I mentioned, having some in-house clinical operations is also very important. A head of clinical operations at the biotech and an in-house group that acts as strategic partners with the CRO to make sure that all deliverables are met is important. I like to use a mixed model for clinical operations where you have some of them in- house and have the team manage the CRO as well.

"We are bringing the CRO in as a partner. We want that partner to be intellectually engaged and not just doing rote management of our study."

What do you ask in your RFP and bid defenses to figure out who you want to work with?

I like the process to be competitive. My standard approach is to bring three CROs in to do competitive bidding. I like to evaluate the teams from each of the CROs. I also try to get commitments that those people won’t roll off the study immediately after you hire them. Disease expertise is critical. I tend to go with people who have a proven track record of success in the disease indication that we are exploring. I also like to see that there is a degree of proactivity on the part of the CRO. We are bringing the CRO in as a partner. We want that partner to be intellectually engaged and not just doing rote management of our study.

It’s also important to consider the indication and the therapeutic area. There are going to be certain CROs that have great expertise with ultra-rare diseases and some of the operational models that can help find those rare patients for your study. If you are working within unusual disease states, you want a CRO that can walk the walk and who talks the talk and really delivers in these indications.

Resources are meaningful too. You want to leverage the competitive process to get a reasonably good deal. That’s where the multiple bids are important. That’s where you can negotiate and bring the cost down.

How do you figure out if potential partners have the expertise or intellectual interest you’re looking for?

We ask the CRO when they pitch and in their subsequent presentations to us to show us evidence of those things. We want them to show us how many studies they’ve done, how they have been successful here and give examples of how they have been proactive and delivered on challenging clinical trials. We may even ask them about challenges they’ve encountered and how they pivoted to a successful strategy.

The other aspect is learning about the individual people that they are proposing to conduct your clinical trial. Hearing about their individual expertise and having each one present their case to you is important as well.

What have you learned since you first started in biotech that can help less experienced CMOs?

I have learned that you have to sweat the details. You have to go through the detailed budgets from the CROs very carefully and really understand what is buried in those budgets. The other aspect is to understand the importance of a competitive bidding process. Also, you need to recognize that the CRO is a true partner. You are forming one team. You must foster that team feeling and energy to get deep investment from the CRO.

One last thing is to use escalation methodologies early and often. Make sure to have quarterly senior management engagements with the CRO to measure the progress of the study and to identify problems early so that they can be fixed early.

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