By Rich Soll, Senior Vice President, Research Service Division, WuXi AppTec (@richsollwx)
With its innovative pipeline of products and distinct approach to R&D, Celgene may have found the industry’s secret sauce to growth and sustainability. Key drivers of that is the three decades-old biopharmaceutical company’s robust investments in early development, its savvy deal-making through highly collaborative approaches with smaller biotechs possessing cutting edge technologies and science, and the hiring of high caliber, enlightened leaders whose unique insights and perspectives present new possibilities for patients, healthcare and society. The net result is impressive – about 50 potential products that could be approved by 2025, and collaborations with more than 30 biotechs in some of the most promising drug development areas, including antibody drugs, gene therapy, and immunotherapy for the treatment of cancer and inflammatory conditions.
I recently had an opportunity to chat with Celgene’s chief scientist Rupert Vessey, executive vice president and president of Global Research and Early Development. Vessey, who joined the company in 2015, couples scientific insights (especially immunology), exposure to novel paradigms, and experiences in early development to steer the helm of Celgene’s R&D engine to deliver its next generation of disease-altering medicines.
Before joining Celgene, Vessey was senior vice president of Early Development and Discovery Sciences at Merck, and held various positions at GlaxoSmithKline in drug discovery, experimental medicine, and early clinical development of therapeutics for respiratory and immune diseases.
“The three companies I’ve worked for – GSK, Merck and Celgene – are extremely different. They’re all trying to solve the same problem, but they have different cultures and different ways of trying to do that. You try to build your pipeline with different types of models. One of the things that really keeps me going at Celgene is, it is a growth environment. This has really been an opportunity to say, let’s apply all that learning and knowledge and let’s try to do some exciting new things and build up a portfolio that will make a difference. We’ve been working hard to do that, and certainly over the next five-to-10 years, hopefully I’ll see those things really transform into a meaningful next generation pipeline for Celgene patients and stakeholders, and that would be spectacular.”
While the stakes are high in the life science arena, Celgene’s ability to embrace and encourage risk-taking has led to many successes for the company and for patients. The company’s transformation, Vessey says, began in 1999 with the repurposing and re-discovery of thalidomide as an oral therapy for patients with a blood cancer called multiple myeloma. The company then built out a class of small molecules and created compounds such as REVLIMID® and POMALYST/IMNOVID® – and then OTEZLA®, which is an oral PDE4 inhibitor.
“Celgene has done a number of things that have been successful,” Vessey says. “For example, deciding to go it alone in Europe, deciding to invest in OTEZLA as a foundational inflammation asset, rather than licensing it out, and then using those foundational molecules and revenue generated from those to invest more broadly in new and next generational opportunities. That’s happened in both hematology and oncology, as well as in inflammation.”
While the company prides itself in taking risks, Celgene has also implemented strategies to minimize those risks, including making informed “go, no-go” decisions early on before spending an enormous amount of money on development, Vessey says.
“Having that early decision-making and having a fairly large number of things to choose from, which we do have, makes a lot of sense,” he says. “One thing’s for sure, if there’s nothing in your pipeline, you’re not going to grow. You have to have some volume so that you have some choices, but they have to be things that you believe early on in the life cycle will have success. And then you have to key up the right experiments to say, OK is it really worth a substantial investment in this or not? I think our ways of mitigating risks are at least some reasonable volume to make choices from and having the right tools and skills to make decisions.”
Celgene also has a knack for unprecedented investments in R&D, and going after really novel, potentially transformational assets, further fueling its pipeline. The company’s most successful therapies, however, have been discovered and developed within its own labs. That’s pretty astounding, considering Celgene has remained fairly small for a biopharma company.
The Power of Partnerships
To complement its tight-knit internal R&D group, Celgene has an extensive network of partners it collaborates with in a deep and integrated way. The company averages about 10-to-11 INDS a year – fewer than half of those come from internals effort, while more than half come from partners. To ensure the success of those programs, however, Celgene works very closely with its partners.
“The pressure for Celgene’s partners to raise money is removed; they can focus on their science, and we let them make their own decisions,” Vessey says of the close collaborations. “They do consult with us, but if they want to have a development candidate or IND candidate, they have the right to decide when to do that, which is very different from the big pharma companies.”
Celgene currently has about 300 clinical trials and 40 partners. To some extent, Vessey says, the company organizes its internal R&D a little differently than a large pharma would in order to bring out the synergies between the partners and the internal organization.
“We do a number of different things,” he says. “Our internal research groups are not focused on specific disease areas; they are focused on what we think are promising areas of science that we have expertise in and we believe could have transformational potential.
“For example, we have a strong interest in an area that we call protein homeostasis, which is really about protein degradation,” he continues. “A lot of that’s built around the platform of oral immunotherapies like REVLIMID. We have made investments in epigenetics, and we’re still trying to work out how to best use the compounds we have, as monotherapies or in combination, through a more translational effort. Our other platform of expertise I would broadly define as immunology, and that applies to oncology, hematology, inflammatory diseases, and now very much toward neuro-inflammation – we see opportunities there and we tend to have a fair number of collaborations that are built around those types of areas of expertise. These collaborations can augment and fill in gaps augmenting our internal research.
Celgene also seeks external partnerships to enter new fields. For example, through its small, internal biologics group, coupled with a network of partners, the company has managed to build capabilities to discover and bring forward biologics molecules against key targets. Celgene has duplicated those efforts in the area of cellular therapies.
Although it’s been a success, Celgene’s extensive partnership model may have been frowned upon a number of years ago. Vessey explains why.
“Historically, a lot of the successful companies just built and built and built, and they had a sort of controlled, ‘not invented here’ environment,” he says. “I think it is difficult to get past that. I don’t think most of the big companies have still quite crossed that divide and don’t truly believe that there are people on the outside that they will invest in who can do it better than they can.”
One of the areas that Celgene has been focused on is hematology, hence the company’s investment in CAR-Ts and bi-specifics. The company is also building a portfolio around inflammation, and has embarked on a mission to build neuroscience into its disease areas and portfolio.
“We hired a team of really experienced neuro people internally, and we think we have both inflammation and protein homeostasis programs and assets that can have real value. So five years from now, I’d definitely like to see a clinical stage portfolio of those things that have promise,” Vessey says.
In terms of milestones for Celgene over the next couple of years, Vessey says the company would like to have its first CAR-T therapy approved in multiple myeloma as well as next generation inflammation therapies.
“We’d like to see a novel protein homeostasis molecule make it into late development, and we have some interesting ones that are in early development that look very promising,” he says. “We’ve also made some big investments in an informatics team in translational work; I’d really like to see those programs accompanied by quality segmentation strategies. We’ve started to do that, and within three years, I look forward to being on top of a range of diseases we’re interested in.”
With a rich early development pipeline, and ample partnerships and milestones to meet, Vessey and his team have quite a bit of work ahead of them. But for Vessey, there’s no place he’d rather be.
“From a personal point of view, the time I’ve spent in the industry has been somewhat unpredictable in many ways, but it’s never been boring, and I’ve always felt that I’m doing something that’s a good contribution,” he says. “I feel really privileged that I’ve had this great opportunity. I knew that when I first stepped into this world that I was embarking on a sort of magical mystery tour, but it’s worked out very well and I am very lucky to have ended up in a position where I can truly make a difference to the patients we serve.”