Where Is J&J Investing For The Future? Cell Therapy, Gene Therapy And RNA
Executive Summary
Janssen global head of R&D Mathai Mammen said the three areas are therapeutic modalities J&J is prioritizing for future drug development, both internally and through partnering.
Johnson & Johnson's Janssen unit is investing in cell therapy, gene therapy and RNA therapeutics as modalities that could deliver highly innovative new drugs, Janssen global head of R&D Mathai Mammen explained while outlining the company's research priorities during a pharmaceutical overview at the company's headquarters in New Brunswick, NJ, on 15 May.
The company also vowed to deliver 10 new drug filings by 2023 across its six therapeutic focus areas: oncology, immunology, neuroscience, cardiovascular/metabolic, infectious disease and vaccines and pulmonary hypertension. (Also see "J&J Plans 10 Potential Blockbuster Filings By 2023 " - Scrip, 15 May, 2019.)
Investors are also thinking about the next wave of drugs J&J will bring forward based on emerging technologies. That is where Mammen said J&J is scouring the horizon and making investments for the future now, both internally and through external partnerships.
"The world continues to uncover validated biological pathways and connect these to unwanted human phenotypes. Many of these will prove actionable through small molecule and monoclonal antibodies," he said. "But a great many others are going to requires new approaches, and sometimes addressing a complex human phenotype demands a complex therapeutic."
Mammen is relatively new to Janssen, having joined to lead global R&D in June 2017 from Merck & Co. Inc., where he was a senior VP at Merck Research Laboratories, responsible for research in cardiovascular, metabolic and renal diseases, oncology/immuno-oncology and immunology. The six-hour pharmaceutical overview was his first one at J&J, since the company last held one in May 2017.
Cell therapy, gene therapy and other gene-editing approaches are quickly becoming an important part of big pharma's development armamentarium as the first drugs developed on all three modalities have reached the market. Nonetheless, the development challenges in each of the areas remains daunting, and the manufacturing and commercial challenges are notable as well. J&J hasn't been as ahead of some peers in areas like immuno-oncology and gene therapy.
"We Believe In Cell Therapy"
In cell therapy, J&J is already developing a B-cell maturation antigen (BCMA)-targeting CAR-T therapy for the treatment of multiple myeloma, where it has a strong foothold with the CD-38 antibody Darzalex (daratumumab). The company is working in partnership with Legend Biotech Corp. to develop the autologous therapy JNJ-68284528, having paid $350m up front under the 2017 collaboration.
The companies announced the initiation of a Phase Ib/II study in the US in relapsed/refractory multiple myeloma in 2018 and said data should be available by the end of 2019 or early 2020. (Also see "J&J Muscles Into CAR-T Field: Initiates Myeloma Studies" - Scrip, 31 May, 2018.) A Phase II study is expected to begin in China in 2019.
Several drug makers are also exploring BCMA targets, however, further ahead in development, most notably Celgene Corp. and bluebird bio Inc., which are developing a CAR-T therapy, and GlaxoSmithKline PLC, which is developing an antibody-drug conjugate. Both of those drugs are on track for filing later in 2019.
Mammen said the first wave of autologous CAR-T therapies, based on individually engineered T-cells, have limitations and J&J is therefore looking to develop off-the-shelf solutions, while also exploring cell therapy for the treatment of solid tumors, where it has had less success than in blood cancers.
"The immediate challenges of creating autologous CAR-T cells lie in making the cell and in all the logistics, and we're investing in every respect here," Mammen said. While he admitted the challenges are immense, he noted, "all in all, we believe in cell therapy. We are committed to being among the leaders in this area in short order."
In Gene Therapy, Starting With Eye Diseases
J&J is also building out in gene therapy, where it hasn't been among the earliest players. Spark Therapeutics Inc. – poised to be acquired by Roche – was the first to bring a gene therapy to the US market with the launch of Luxturna for inherited blindness, and Novartis AG is expected to bring the second shortly, Zolgensma, pending at FDA for spinal muscular atrophy. Pfizer has invested substantially in gene therapy and has built out a pipeline of drugs in clinical development.
J&J expanded its capabilities in gene therapy through a partnership with MeiraGTx Holdings PLC in January, gaining rights to clinical-stage candidates for inherited retinal disease in exchange for $100m up front. (Also see "MeiraGTx Signs J&J To Develop Gene Therapies For Rare Retinal Diseases" - Scrip, 31 Jan, 2019.) But Mammen said the company has also been working internally and has plans to expand beyond ophthalmology.
"We're beginning in the eye for a variety of reasons. First, we have line of sight to vision-restoring medicines for retinal diseases. Second, we have with Meira very importantly sound and reliable manufacturing at the scale needed for the eye." J&J plans to expand to other therapeutic areas, but will do so in a disciplined way, understanding the need to build large-scale manufacturing in parallel.
Lastly, Mammen highlighted siRNA as an area targeted for investment and pointed to J&J's partnership with Arrowhead Pharmaceuticals Inc., under which the companies are developing a gene-silencing candidate for hepatitis B infection. (Also see "J&J Bets Big On Arrowhead’s Early Promise In Hepatitis B" - Scrip, 4 Oct, 2018.)
"We plan on exploring additional applications across therapeutic areas with siRNA, and we see a future to nucleic acid therapeutics that can also involve messenger RNA, replicating RNA and gene editing," he said. "We appreciate that delivery is a very significant problem, perhaps the problem to solve, and we're working very hard here with our partners to make progress."
The company will invest internally and externally, Mammen said, claiming that the biotech ecosystem is "thriving."
"To thrive in tomorrow's marketplace, a successful large pharmaceutical company must understand how to be an integral part of this ecosystem and not just compete against it," he said. The company has built a reputation for partnering, he added, pointing to a willingness to be flexible when it comes to licensing technology, collaborating with partners, incubating new companies, or buying an asset or company outright.
"We are a participant, a partner and an accelerator inside this vibrant ecosystem," he said.