With the success of CAR T-cell therapies and other innovative medicines in this area, immuno-oncology has become a buzzword in biotech, with more and more companies starting up in Europe and elsewhere. With so many players involved, it can be hard to know who is doing what. Here are 20 European companies we think stand out and are leading the revolution in cancer medicine.

Although immunotherapies to treat cancer have been around for decades, new approaches are popping up every other day. After all, enlisting the immune system to fight cancer remains an extremely promising therapeutic strategy. There are so many companies focusing on different kinds of immunotherapies that it was quite a challenge to choose our favorites. We therefore enlisted the help of experts in the industry to select the following 20 immuno-oncology companies in Europe as our top picks. As ever, these are in no particular order.

Founded in Abingdon, UK, in 2008, Adaptimmune develops enhanced T-cell therapies that support the immune system in detecting and targeting cancer cells. Interestingly, its SPEAR T cell technology can target a variety of solid tumors a feat that is not easy to achieve, as solid tumors have a highly complex tumor microenvironment that many immunotherapies find difficult to penetrate.

The companys technology can identify and select T cell receptors (TCRs) that are more likely to improve the patients immune response and result in the effective binding of cancer cells. In January 2020, Adaptimmune and Japanese company Astellas agreed to co-develop and co-commercialize stem-cell-derived allogeneic chimeric antigen receptor (CAR)-T and TCR T cell therapies, which means that they not only treat one specific patient but a large number of patients with a particular cancer type. The deal was worth 806M.

ADC Therapeutics works in the area of antibody-drug conjugates (ADCs). Since being founded in 2011 in Lausanne, Switzerland, ADC Therapeutics has raised 514M ($558M) to advance its immuno-oncology therapies. The companys proprietary ADCs combine monoclonal antibodies that are specific to targets on the surface of tumor cells with a specific class of toxins called pyrrolobenzodiazepine (PBD) dimers.

The PBD dimer is released inside the tumor cells and binds to the tumor DNA, which blocks the division of the tumor cells and eventually kills them. ADC Therapeutics currently has two ADCs for liquid tumors in pivotal phase II studies, and one ADC targeting solid tumors in phase Ib. In January 2020, the company announced the positive results of its phase II trial of its leading ADC in patients with relapsed or refractory diffuse large B cell lymphoma.

Yet another direction in the treatment of cancer via the immune system is taken by Heidelberg-based company Affimed Therapeutics. Founded in 2000, the company focuses on the innate immune system. Using its ROCK platform, Affimed develops multi-specific antibodies called cell engagers.

Innate cell engagers can bind to the patients innate immune cells, including natural killer cells and macrophages, while simultaneously binding to specific tumor cells. As a result, the patients own immune systems can attack and kill the cancer cells. The companys lead candidate is currently in phase II for a number of liquid tumors.

Based in London, UK, and founded in 2014 as a spin-out from the University College London, Autolus Therapeutics uses CARs and TCRs to reprogram T cells so they recognize and consequently kill tumor cells. In January 2020, the company revealed the closure of its public offering on the Nasdaq with net proceeds of 68.4M ($74.2M).

Autolus other news in January was the announcement of the clinical progress of its next-generation programmed T cell therapy. It is currently in Phase I/II for the treatment of adults with relapsed or refractory diffuse large B cell lymphoma. The results showed no neurotoxicity and a manageable safety profile.

BioNTech has a much larger pipeline that contains CARs, TCRs, recombinant cytokines, and optimized mRNA. Founded in Mainz, Germany, in 2008, the company is one of the largest biotechs in Europe. Its pipeline is full to bursting with a variety of immuno-oncology therapies based on mRNA, antibodies, and CAR-T cells.

In July 2019, BioNTech raised one of the biggest ever funding rounds of a European biotech with a whopping 290M Series B. However, in October of that same year, the companys Nasdaq IPO, which was initially estimated to raise around 725M, resulted in pricing at only 141M due to poor market conditions in the US.

Based in Paris, France, and founded in 1999, Cellectis is also focusing on CART-cell therapy. It is working on a novel type of CART therapy known as Universal CARTs (UCARTs). Unlike the two approved CAR-T therapies, Novartis Kymriah and Gileads Yescarta, UCARTs are allogeneic so rather than being personalized, they can treat a large number of patients with a particular cancer type.

In November 2019, Cellectis announced that it had won the European patent challenge for the use of CRISPR-Cas9 for gene editing T cells. This process will help the company further develop its UCART platform. To date, six of its main UCART product candidates are in Phase I clinical trials.

As another biotech giant, Celyad is also working in the field of CART-cell therapies but is focusing on the NKG2D receptor. Founded in 2004 in Mont-Saint Guibert, Belgium, the companys lead immuno-oncology candidate uses the NKG2D receptor. NKG2D can bind to eight different ligands that are naturally found on cancer cells present in 80% of solid and liquid malignancies.

Something cool about NKG2D is that the ligands that it recognizes are also expressed by the tumor microenvironment, which comprises the blood vessels that support the tumor and the cells that make sure the tumor can evade the immune system. As a result, the lead candidate can target and kill the tumor as well as cleaning up its microenvironment. The candidate is currently in phase I.

Spun-off from the Babraham Institute in Cambridge, UK, in 2007, Crescendo Biologics develops targeted T-cell enhancing therapeutics with the aim of tackling difficult-to-treat cancers. The companys Humabody therapies are small, multi-specific antibody fragments that can penetrate tumor tissue in a way that conventional antibodies cannot.

Crescendo Biologics lead proprietary candidate is a bispecific T-cell engager targeting the prostate-specific membrane antigen. It can selectively activate tumor-specific T cells within the tumor microenvironment. It is currently advancing towards clinical development.

As a spring chicken among other European immuno-oncology companies, we felt Ervaxx deserved a mention here because it develops cancer vaccines and cell therapies targeting dark antigens normally silent genes that are expressed in cancer cells. Founded in 2017 in London, UK, Ervaxx recently made headlines when it got its hands on the license of an exciting new preclinical stage universal cancer immunotherapy.

In early January 2020, a group of researchers at Cardiff University discovered a new type of T cells that have the potential to attack a wide range of cancers, such as leukemia and melanoma. Ervaxx is continuously expanding its repertoire of Dark Antigens. Using these, the company is working on a pipeline of off-the-shelf cancer vaccines and TCR-based therapies.

Founded in 2008 in Copenhagen, Denmark, Evaxion takes a very different approach to fighting cancer: using artificial intelligence (AI) to develop immunotherapies. The company has developed two AI platforms that can identify and optimize epitopes and antigens that are capable of eliciting strong immune responses against cancer and infectious diseases.

The companys PIONEER platform is used for the development of personalized cancer immunotherapies. In April 2019, it announced the beginning of phase I with the dosing of the first patient with its lead candidate, a therapeutic vaccine. Evaxion closed the year by successfully raising 16M ($17M).

GammaDelta Therapeutics, founded in 2016, takes another approach to immuno-oncology therapies. The London-based company focuses on gamma delta T cells. Unlike alpha beta T cells which are commonly used in CAR-T therapy, gamma delta T cells are a part of the innate immune system. In short, this means that gamma delta T cells are already pre-programmed to identify and kill cells that are modified by cancer. The company is currently advancing its allogeneic gamma delta T cell therapies through preclinical development.

In October 2019, GammaDelta Therapeutics announced the formation of the spinout company Adaptate Biotherapeutics. Adaptate will be developing therapeutic antibodies that can modulate the activity of gamma delta T cells with the aim of triggering an immune response to fight cancer.

Danish biotech Genmab had an exciting start to the new year. In January 2020, one of the companys lead candidates daratumumab, a monoclonal antibody, received marketing authorization by the EMA. Marketed as DARZALEX, it can be used in combination with bortezomib, thalidomide, and dexamethasone to treat multiple myeloma.

Founded in Copenhagen in 1999, Genmab focuses on the development of antibody therapies against cancer. In December 2019, Genmab signed a deal with German biotech CureVac to develop mRNA drugs that can produce antibodies within the patient, which is an exciting development.

Heidelberg Pharma, formerly known as Wilex, was founded in 1997 in Heidelberg, Germany. The company focuses on ADCs. It has an exclusive license agreement with the Max Delbrck Center for Molecular Medicine in the Helmholtz Association in Berlin that includes a number of surface proteins found in multiple myeloma cells called B cell maturation antigen (BCMA).

Heidelberg Pharmas lead candidate targets BCMA and is currently advancing through the preclinical stage. It is an ADC that consists of a BCMA antibody, a specific linker, and the toxin amanitin, one of the deadliest toxins found in several mushroom species.

Founded in 2011, Austrian company Hookipa Pharma engineers arenaviruses to deliver tumor-specific genes to dendritic cells. Dendritic cells naturally activate killer T cells by delivering the tumor-specific antigens to them, which triggers an immune response. HOOKIPA Pharmas co-founder, Rolf Zinkernagel, actually received the Nobel Prize for Physiology or Medicine in 1996 for his work on how killer T cells can recognize virus-infected cells.

Hookipas leading immuno-oncology therapy is currently progressing through phase I. In February 2019, the company closed a Series D financing round for 33.2M ($37.4M). The funding is being used to boost the clinical development of its immunotherapies for cancer and infectious diseases based on its proprietary arenavirus platform.

This French company develops antibody therapies to fight cancer. Marseille-based ImCheck has developed a pipeline of monoclonal antibodies that target specific checkpoint molecules of the butyrophilin (BTN) family, which engage gamma delta T cells. As part of the innate immune system, gamma delta T cells fight cancer cells naturally.

ImChecks lead drug candidate, an anti-BTN3 antibody that targets solid tumors, is expected to enter phase I in 2020. In order to fund this trial and further boost the development of immunotherapies, ImCheck closed a series B funding round in December 2019 worth 48M.

Immatics was founded in 2000 in Tbingen, Germany. The company develops personalized immuno-oncology therapies by engineering patient T cells to express TCRs, which specifically target the patients cancer. Unlike CAR-T therapies that generally target surface proteins, Immatics immunotherapy can also target proteins within cancer cells, which makes the cancer cells more vulnerable and accessible to the immune system.

In August 2019, American company Celgene and Immatics signed a deal worth more than 1.35B ($1.5B) to further develop its immuno-oncology therapies. In three cancer immunotherapy programs, Immatics will develop leading cell immunotherapy candidates for solid tumors, while Celgene has the option to co-develop the candidates or take over the development altogether.

Based in Oxfordshire, UK, and founded in 2008, Immunocore also focuses on TCRs. Its ImmTAC (immune mobilizing monoclonal TCRs against cancer) technology is based on a new class of bi-specific biologics that can activate a specific T cell response in cancer cells.

In December 2019, Immunocore announced the start of the first-in-human clinical trial of its third bispecific, which was developed using the ImmTAC technology platform. Immunocore has collaborations with a number of partners, including AstraZeneca, Genentech, GSK, and Eli Lilli.

Medigene also focuses on TCRs. However, this company develops modified TCRs called TCR-Ts, as well as dendritic cell vaccines (DCs), and T cell-specific antibodies (TABs).

In January 2020, Medigene announced positive results after a two-year phase I/II for its DC vaccine in patients with acute myeloid leukemia (AML). Moreover, its leading TCR-T candidate is currently being prepared for phase II clinical trials. Medigene was founded in 1994 in Martinsried, Germany.

As a neighbor of Medigene, MorphoSys is also based in Martinsried, Germany. It was founded in 1992. The company is one of the very few European biotechs valued at over 1B. MorphoSys develops antibody therapies for numerous conditions.

The companys lead immuno-oncology candidate tafasitamab is a humanized monoclonal antibody that targets CD19, an antigen mainly expressed by various B cell-derived blood cancers, such as non-Hodgkins lymphoma, diffuse large B cell lymphoma, and chronic lymphocytic leukemia. This candidate is being co-commercialized by Imcyte. Other partners of MorphoSys include Novartis, Roche, GSK, and Roche.

Another company focusing on ADCs is NBE Therapeutics. This companys goal is to target solid tumors. Based in Basel, Switzerland, and founded in 2012, NBE Therapeutics has developed a technology that uses an enzyme to attach small molecule drugs to monoclonal antibodies. This approach is different from conventional ADCs that are usually generated using a chemical junction, which can be unstable at times.

The companys lead candidate, an ADC for the treatment of triple-negative breast cancer, lung, and ovarian cancer, is expected to reach phase I in 2020.

Images via Elena Resko & Shutterstock.com

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