Cell therapies: opportunities and challenges

May 5, 2020 Article V-Bio Ventures

This article was authored by Christina Takke from V-Bio Ventures.

Recent activities in the cell therapy field have prompted many investment funds to pour fresh and increasing capital into this space. In this review, we share some observations and highlight a few of the questions that arise when new modalities cross the bridge from bench to bed.

New genetic and cellular modalities hold the promise of not only ameliorating but potentially even curing some, until now, untreatable diseases. In December 2019, Coherent Market Insights published a staggering global market estimate for cell therapy, which they valued at over USD 7 billion in 2018. They predicted an annual growth rate of 21.1% over the next few years, in which case the market will surpass USD 40 billion by 2027.

However, one needs to keep in mind that cell therapies have been around for many years. Bone marrow transplants were pioneered by a team at Fred Hutchinson Cancer Research Centre, led by the Nobel Prize winner E. Donnall Thomas, between the 1950s to 1970s. Today, bone marrow transplants are commonly used to treat patients with certain forms a blood cancer, as well as congenital blood disorders. These therapies can consist of autologous cells (the patient’s own cells) or allogenic cells (cells coming from a donor).

Over the past several decades, scientists have worked hard to increase the efficacy of these therapies in eliminating the patient’s cancer cells. They have also worked hard on the logistical challenges associated with a treatment that has yet to be made into an “off the shelf” therapy.

CAR T cell therapy

CAR T cell therapy is a type of treatment in which a patient’s T cells are changed in the laboratory so they will attack cancer cells. In practice: T cells are taken from a patient’s blood, then the gene for a specific receptor (called a chimeric antigen receptor (CAR)) is added in the laboratory, so that the T cells will bind to a surface protein on the patient’s cancer cells. The T cells are then multiplied and given back to the patient.

“At V-Bio Ventures, we feel that a company developing new therapeutic modalities needs to own or control the entire manufacturing process, enabling it to be master of its own destiny.”

Two engineered CAR T cell therapy products are on the market today: Yescarta, a treatment for large B-cell lymphoma (BCL) from Gilead/Kite Pharma; and Kymriah, for B-cell acute lymphoblastic leukaemia (ALL), from Novartis.

The approval of these two treatments has unlocked a real wave of new investments into early stage cell therapy companies. It has also prompted more pharma/biotech acquisitions, including Astellas which acquired both Xyphos biosciences and Universal Cells at a pre-clinical IND stage. Two further M&A deals that are yet to be put into effect include: Kite Pharma (a subsidiary of Gilead), which has a research partnership with, and an option to acquire, Gadeta; and Takeda Oncology, which has a research partnership with, and option to acquire, GammaDelta Therapeutics.

Additional product launches in the coming years will, in our view, further heat up the market and contribute to boosting the demand for CAR T cell therapies.

What comes after CAR T?

The first cell therapy programs were all immunotherapies aimed at fighting cancer. This was a logical first step for the industry, as safety aspects are less of a concern for cancer indications as compared to the chronic treatment of (relatively healthier) autoimmune patients.

Recently, though, the T cell therapy scope has been broadening to include these more chronic diseases. Scientists are expanding their horizons and are looking at other cell populations, such as B cells, NK cells and regulatory T cells. Mechanistically, regulatory T cells have the opposite effect of CAR T cells and can therefore suppress, rather than enhance, the body’s immune response.

This new expansion of the field is already attracting the interests of investors. Since January 2020, BioCentury has published the launch of two new companies in this space: Sonoma Biotech and Kyverna Therapeutics. Both are T cell therapy companies targeting autoimmune diseases, and launched with a Series A round of USD 40 million and USD 25 million, respectively.

“Not only innovative research and human talent is required to maintain a successful biotech hub; ancillary supporting structures, such as access to lab space or adequate manufacturing capacities, are also essential to anchor the next generation of biotech companies.”

The technical challenges that lie ahead

Science is paving the way, but for cell therapies to become real game changes, many challenges still remain. We feel that both interdisciplinary and international approaches are needed, if the industry is to solve several scientific, manufacturing and patient selection questions.

Technical challenges, in a nutshell:

  1. Understanding the mechanism by which stem cells work will be key. Developing reliable animal models for testing pre-clinical safety and efficacy remains a serious challenge; the way human cells behave in animal models might not perfectly mirror the human-human situation.
  2. Understanding the patient selection, in view of identifying patients that will benefit from one of the expensive new treatments, is crucial to enabling commercial success. Recent literature data and research from Genentech has opened a new avenue for a non-invasive diagnostics.
  3. Companies need to clearly define the product. Most of the new cell therapies consist of living cells, which react to various environmental signals and will change their appearance and characteristics depending on the way they are produced and stored, as well as changing within the patient receiving those cells. 

The other big hurdle: Manufacturing and Quality Control

Production has always been a challenge for new drug modalities. Besides the cost-effective production of the biological material, the companies need to prove the homogeneity of their product and define the exact threshold for potential deviations and impurities.

This is particularly true for cell therapy products, given their living nature and complexity. This difficult task has been widely recognised, with several cell therapy companies building out their own manufacturing capabilities, or accessing proprietary slots with service organisations, as well as investing in advanced analytical cell typing methodologies.

Venture Capital (VC) investors are willing to fund new developments generating (pre-) clinical data to substantiate the potential of the invention. However, putting VC money in bricks and mortar, or in this case in steel tanks and expensive pieces of hardware, is a recurring dilemma and to date less attractive for financially driven VCs.

“The product is the process and the process is the product” still holds true for all new treatment modalities beyond protein drugs and small chemical molecules.

At V-Bio Ventures, we feel that a company developing new therapeutic modalities needs to own or control the entire manufacturing process, enabling it to be master of its own destiny. Constant access to production modules is required to be able to run the various iterations of process improvement in a timely manner.

Read this previous BioVox article for more on the future of cell therapy.

How to finance this expensive development?

Taking the above into account, a crucial question remains for young companies: how to finance this expensive testing, manufacturing and quality control? Only creative financing solutions will allow innovative start-up companies to quickly advance their new treatment modalities into clinical trials and to eventually reach the patients who need them.

Looking at this from another perspective: enabling manufacturing expertise and production capacity in a cluster can also boost the local biotech ecosystem in a broader sense. It will anchor innovative research and development companies to the area and enable further growth of the cluster. Christina Takke, Managing Partner of V-Bio Ventures, concluded:

“Not only innovative research and human talent is required to maintain a successful biotech hub; ancillary supporting structures, such as access to lab space or adequate manufacturing capacities, are also essential to anchor the next generation of biotech companies.”


V-Bio Ventures
V-Bio Ventures

We are a life sciences fund investing throughout Europe in start-up and early-stage companies with high growth potential. Our articles cover investment-related topics in life sciences, including innovation trends, the latest business themes and exciting updates on our portfolio companies.

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