CAR-T companies are on the rise, supported by growing investment flowing into CAR-T research, landmark approvals of CAR-T cell therapies by the U.S. FDA (Kymriah and Yescarta), and major acquisitions within the CAR-T space. Most notably, Celgene snagged Juno Therapeutics for a shocking $9 billion in January 2018 and Gilead acquired Kite Pharma for an astounding $11.9 billion in August 2017. Chimeric antigen receptor T-cell therapy (CAR-T) is an approach that is now being explored as an alternative to conventional treatments for several forms of cancer.
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Definition of CAR-T
Chimeric antigen receptors (CARs) are defined as genetically engineered allogeneic cells that are developed in the laboratory and infused into a patient to help in detecting and fighting cancer cells. The protein constructs stimulate anti-cancer T-cells which in turn boost a patient’s immune system.
Medicine continues to be greatly revolutionized by the continuous advancements in both treatment and technology. What is capable of being done today, would have been previously unfathomable. A example of this is the rise of CAR-T cell therapies, as biotechnology companies hunt out ways to revolutionize cancer treatments and resolve basic challenges that have restricted patient care for years.
Highlighted below are leading CAR-T companies that are involved with chimeric antigen receptor (CAR-T) cell technologies. Some of the companies are developing CAR-T therapies in house, while others have invested in, acquired, or merged with companies developing CAR-T therapies.
In June 2018, AbbVie (NYSE: ABBV) and Calibr, a nonprofit drug discovery division of Scripps Research, announced they will co-develop CAR-T therapies aimed at solid tumors and other cancers. Under the terms of the license agreement, AbbVie will pay Calibr an undisclosed upfront license fee and gain exclusive access to Calibr’s switchable CAR-T platform for up to four years.
Launched April 2018, Allogene Therapeutics was formed by two former Kite Pharma executives and raised $300 million in investor funds to acquire and advance a portfolio of cell therapies previously controlled by Pfizer. Allogene will receive from Pfizer the rights to 16 preclinical CAR T assets licensed from Cellectis and Servier and one clinical asset licensed from Servier, UCART19, an allogeneic CAR T therapy that is being developed for treatment of CD19-expressing hematological malignancies. In partnership with Servier, UCART19 is initially being developed in acute lymphoblastic leukemia (ALL) and is currently in Phase I. UCART19 utilizes TALEN® gene editing technology pioneered and owned by Cellectis. As a result of the deal, Pfizer will have a 25% ownership stake in Allogene.
Since January 2015, Amgen and Kite Pharma have strategic partners in the development and commercialize CAR-T cell therapies based on Kite’s engineered autologous cell therapy (eACT™) platform and Amgen’s broad array of cancer targets. The collaboration combines Amgen’s immuno-oncology assets with Kite’s industry dominance in CAR T cell therapy sector.
Agios is focuses on developing small-molecule anticancer therapeutics targeting cancer cell metabolism through the growth factor pathway. Agios had a broad parternship with Celgene that assisted its ability to have a July 2013 IPO in which it become a publicly traded company (NASDAQ: AGIO). In May 2016, it then entered a $200 million deal with Celgene to to develop therapeutics that impact cellular metabolism and explore immuno-oncology drug prospects.
Atara Biotherapeutics (Nasdaq: ATRA) is an off-the-shelf, allogeneic T-cell immunotherapy company developing treatments for cancer, autoimmune and viral diseases. Originating from clinical experience at Memorial Sloan Kettering and QIMR Berghofer, Atara’s off-the-shelf, allogeneic, T cells are bioengineered from donors with healthy immune function and allow for rapid delivery from inventory to patients without a requirement for pretreatment. Atara Biotherapeutics is building a $55M, 90,000-sq-ft CAR-T manufacturing facility in Thousand Oaks, California, that will be completed in 2019.
Autolus Ltd. develops T-cell therapies that utilize advanced cell programming and manufacturing technologies. Founded on advanced cell programming technology that was pioneered by Dr Martin Pule, it was spun-out and established as an independent company by University College London in 2014. It has a development-stage pipeline of products for the treatment of haematological malignancies and solid tumors. In September 2017, CAR-T specialist Autolus raised $80 million in its third-round financing, bringing the total financing raised by Autolus to approximately $173 million. On June 26, 2018, Autolus announced that its IPO also raised $150 million.
Located near the Houston Medical Center in Texas, Bellicum Pharmaceuticals focuses on developing innovative cellular immunotherapies for cancers and blood disorders. Its GoCAR-T technology incorporates a switch that activates CAR T cells when triggered by both rimiducid and the targeted antigen expressed on the surface of the cancer cells. GoCAR-T cells are designed to only be fully activated when exposed to both the cancer cells and rimiducid, a system designed to control the degree of activation of the CAR-T cells through adjustments in rimiducid administration.
bluebird bio has an integrated product platform encompassing cancer immunotherapy, gene therapy and gene editing. In partnership with Celgene, it is developing bb2121, a CAR-T therapy targeting b-cell maturation antigen (BCMA) in previously treated patients with multiple myeloma. bb2121 has Breakthrough Therapy Designation with the FDA and PRIME (PRIority MEdicines) eligibility by the EMA.
In June 2018, Calibr, a nonprofit drug discovery division of Scripps Research, announced a collaboration to develop CAR-T therapies in partnership with Abbvie. Calibr’s novel cell therapy program, led by Travis Young, Ph.D., Director of Protein Sciences at Calibr, is designed to “enhance safety, versatility and efficacy through a proprietary modular ‘switchable’ CAR-T cell that uses antibody-based switch molecules to control the activation and antigen specificity of CAR-T cells.” Calibr’s proprietary technology may be capable of enabling universal CAR-T-based treatments across a variety of hematological and solid tumor indications.
CARsgen Therapeutics (CARsgen) is commercializing chimeric antigen receptor T-cell (CAR-T cell) therapies for solid tumors and and hematology malignancies. Its pioneering CAR-T cell therapies include: anti-GPC3 CAR-T for hepatocellular carcinoma (HCC), anti-GPC3 CAR-T for squamous lung cancer (SLC), cancer-specific anti-EGFR CAR-T for glioblastoma multiforme (GBM) and first-in-class anti-Claudin18.2-CAR-T for gastric and pancreatic cancer. In July 2017, its anti-Claudin18.2 CAR-T cell therapy began a Phase I clinical trial and started patient recruitment at Changhai Hospital of Shanghai, a Chinese hospital with a specialty in gastroesophageal and related cancers.
An American biotechnology company, Celgene grabbed the spotlight when it acquired Juno Therapeutics for $9 billion in January 2018 in a strategic move to acquire full rights to the bluebird bio’s CAR-T program. In December 2017, Celgene’s research partner bluebird bio also released promising results for its CAR-T product bb2121 in multiple myeloma patients.
A French biopharmaceutical with offices in Paris and New York, Cellectis develops genome-edited chimeric antigen receptor T-cell technologies for cancer immunotherapy. It is creating “off-the-shelf” allogeneic products it calls UCART (Universal Chimeric Antigen Receptor T-cells). UCART19 is its allogeneic anti-CD19 CAR T-cell product being developed by Servier and Pfizer. UCART123 is its product candidate for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Cell Design Labs
Headquartered in Emeryville, California, Cell Design Labs was acquired by Gilead Sciencesin December 2017. In the deal, Gilead acquired all of the outstanding shares of Cell Design Labs, including the 12.2% of shares held by Gilead subsidiary Kite Therapeutics, for up to approximately $567 million. Cell Design Labs is a biotherapeutics company on a mission to discover and build the next generation of anti-cancer therapies, using two unique technology platforms: Throttle™ (an “on/off” switch that allows the control of CAR T-cell activity using small molecules) and synNotch™ (a synthetic gene expression system that can be deployed to engineer CAR-T cells that require dual antigen recognition for activation).
Celularity is looking to solve ottleneck in the CAR-T industry by deriving T-cells from a single (allogeneic) cell line, potentially positioning itself to slash the price point for CAR-T treatments. Celularity’s medicine asset portfolio consists of more than 200 issued or pending patents, as well as pre-clinical and clinical assets, including CAR constructs for allogeneic CAR-T/NK products and licenses of 100+ immunotherapy assets.
Celyad is a clinical-stage biopharmaceutical that is developing next generation CAR-T NK cell-based immunotherapies for cancer treatment. The Belgium-based biopharmaceutical holds U.S. Patent No. 9,181,527 relating to allogeneic human primary T-Cells that are engineered to be T-Cell Receptor (TCR)-deficient and express a Chimeric Antigen Receptor (CAR). Its unique immunotherapy approach emerged from research conducted by Professor Charles Sentman and his team at Dartmouth College, called the NKR-T platform.
Fate Therapeutics is developing FT819 as an off-the-shelf CAR T-cell product candidate produced from a master induced pluripotent stem cell (iPS cell) line. It has two targeting receptors, a chimeric antigen receptor (CAR) targeting CD19-positive tumor cells and a CD16 Fc receptor that can engage other cancer therapies, such as tumor antigen-targeting monoclonal antibody (mAb)-based treatments, to overcome antigen escape.
Fortress Bio is involved in the CAR-T space through its subsidiary Mustang Bio, a clinical-stage biopharmaceutical company that is developing CAR-T technologies with a strategy that is heavy on in-licensing, acquiring an ownership interest, funding third-party R&D, or outlicensing its technologies to bring them to market.
One of the best capitalized and most aggressive players in the CAR-T space, Gilead acquired Kite Pharma for an astounding $12 billion in August 2017. Shortly thereafter in October 2017, Gilead Sciences company Kite Pharma became the second company to achieve a CAR-T cell therapy approval by the U.S. FDA (Yescarta), getting Yescarta approved for the treatment of relapsed or refractory large B-cell lymphoma in adult patients. More recently, Gilead acquired Cell Design Labs in a deal valued at $567 million to further expand its CAR-T product development portfolio.
Janssen Biotech has entered into a global partnership and collaboration with Legend Biotech with an aim of manufacturing and commercialising experimental CART-cell therapy LCAR-B38M. The therapy is targeted towards treating Multiple Myeloma.
Founded in 2013, Juno Therapeutics was acquired by Celgene Corporation for an astounding $9 billion in January 2018. Juno Therapeutics is a clinical-stage immunotherapy company that is revolutionizing medicine by re-engaging the body’s immune system to treat cancer. Juno’s pipeline of investigation CAR T cell product candidates applies its CAR and TCR technologies against a variety of cancer targets.
Headquartered in Shanghai, China, JW Therapeutics was founded in 2016 as an innovative CAR-T start-up. It was cleverly named “JW” Therapeutics to reflect that it was formed through collaboration by Juno Therapeutics (now owned by Celgene) and WuXi AppTec, combining Juno’s CAR-T platform with WuXi AppTec Group’s R&D and manufacturing. In March 2018, JW Therapeutics announced it had secured in $90 million in Series A financing to support its progress toward a CAR-T clinical trial. It boasts an impressive investor list that includes: Temasek, Sequoia Capital China, YuanMing Capital, as well as Oriza Seed Capital, Yipu Capital, AVICT Global Holdings, and existing investors WuXi and Juno.
A Gilead Sciences company, Kite Pharma was the second company to achieve a CAR-T cell therapy approval by the U.S. FDA (Yescarta). Priced at $373,000 per patient, Yescarta is for relapsed or refractory large B-cell lymphoma adult patients.
Medisix Therapeutics Pte Ltd.
Medisix is a Singapore-based immune engineering start-up developing novel cellular therapies to address T cell malignancies. Its technology platform originates from world expert in translational immunology, Professor Dario Campana, MD, PhD, a physician scientist who pioneered CAR-T biology. Its programs utilize proprietary immune engineering approaches that enable T cell leukemias and lymphomas to be targeted with cell therapy. It announced the close of a USD $20 million Series A financing on May 14, 2018.
Mustang Bio (NASDAQ:MBIO) is a Fortress Biotech, Inc. (NASDAQ:FBIO) company that specializes in the development of novel immunotherapies based on proprietary CAR-T technology. In October 2017, it entered into a lease agreement with the UMass Medicine Science Park in Worcester, MA, for a manufacturing facility to develop its CAR T product candidates. In addition to its CAR T pipeline, Mustang partnered with the City of Hope National Medical Center and the Fred Hutchinson Cancer Research Center to develop CAR-T therapies for various cancers, and with Harvard Medical School’s Beth Israel Deaconess Medical Center and the Harvard Stem Cell Institute (HSCI) to support the development of CRISPR/Cas9-enhanced CAR T therapies for hematologic malignancies and solid tumors.
Nanjing Legend Biotech
Chinese Firm Nanjing Legend Biotech has developing a strong pipeline of CAR-T products to treat solid and liquid tumors. Johnson & Johnson agreed to pay $350 million to partner with the firm after the its released promising CAR-T data at the ASCO annual meeting.
Novartis (NYSE:NVS), a global leader in integrated cancer solutions, achieved a world-first Kymriah became the first CAR-T cell therapy to be approved by the U.S. FDA. With a price tag of $475,000, Kymriah is a treatment for B-cell acute lymphoblastic leukemia that uses autologous (self-derived) T cells. The Swiss multinational pharmaceutical is noted to be one of the largest pharmaceutical companies by both market cap and sales.
Pfizer (NYSE:PFE) has partnered with Cellectis and Servier to co-develop allogeneic CAR-T cell therapies for multiple indications. Cellectis’ CAR-T platform technology is an allogeneic approach to CAR-T cell therapies that aims to produce genetically engineered immunotherapy treatments. Through a partnership with Servier, Pfizer is co-developing UCART19 in the U.S., an investigational allogeneic CAR-T cell therapy involving T cells from healthy donors. UCART19 appears bind to the CD19 antigen on the surface of B cells and is believed to elimiante CD19 positive cells through T-cell mediated pro-inflammatory cytokine production and cytotoxicity. In November 2017, Pfizer and Servier presented preliminary results from two phase 1 trials with UCART19 at the ASH Annual Meeting.
In February 2016, Baxalta and Precision BioSciences announced they were partnering to develop allogeneic CAR-T therapies in a collaboration that could generate up to $1.6 billion for Precision. Precision BioSciences’ proprietary ARCUS genome editing technology enables the production of CAR T cells derived from healthy donors rather than relying on a patient with a disease, a strategy that could overcome manufacturing limitations associated with existing CAR T therapies. In June 2016, Shire completed a $32 billion merger with Baxalta.
Poseida’s pipeline is composed of six preclinical and clinical programs involving gene therapy and CAR-T product candidates for orphan diseases and cancer. P-PSMA-101 is Posieda’s PSMA-specific stem cell memory CAR-T drug candidate for the treatment of prostate cancer, the most common cancer among men in the U.S.
A French pharmaceutical company, Servier entered the CAR-T market in 2015 when it acquired the rights to UCART19 from Cellectis.
In June 2016, Shire completed a $32 billion merger with Baxalta. Only months before in February 2016, Baxalta and Precision BioSciences entered an agreement to develop allogeneic CAR-T therapies in a collaboration worth up to $1.6 billion. Precision BioSciences’ proprietary ARCUS genome editing technology enables the production of CAR T cells derived from healthy donors rather than relying on a patient with a disease.
Sorrento is developing a proprietary non-viral chimeric antigen receptor (CAR)-T technology that could impact the way that CAR constructs are integrated into T cells. Its anti-CEA CAR-T has shown promising clinical activity and safety in phase IB clinical trial.
Ziopharm’s immunooncology programs, in collaboration with Intrexon Corporation (NYSE:XON) and the MD Anderson Cancer Center, include CAR-T and other adoptive cell-based approaches that leverage non-viral gene transfer methods. ZIOPHARM is advancing its non-viral Sleeping Beauty (SB) platform towards point-of-care (P-O-C) for rapid manufacturing of genetically modified CAR+ T cells, with data from 1st and 2nd generation SB clinical trials indicatng safety, tolerability, disease response, long-term survival, and persistence of CD19-specific CAR+ T cells.
List of CAR-T Companies
A list of CAR-T companies is included below:
|Company Name||CAR-T Technnology||Disease Targets||Country||City|
|AbbVie||“Switchable” CAR-T treatments co-developed by Calibr||Solid tumors and other cancers||USA||Chicago|
|Agios Pharmaceutical||Modulating cellular metabolic pathways to enhance the immune system’s ability to attack tumors||Metabolic immuno-oncology||USA||Boston|
|Allogene Therapeutics||UCART19 (and other CAR-T assets from Pfizer)||Hematological malignancies; Acute lymphoblastic leukemia (ALL)||USA||San Francisco|
|Amgen||eACT™ technology platform||Hematological and solid tumor indications||USA||Thousand Oaks|
|Atara Biotherapeutics||Licensed technology creates T-cells broadly targeted to recognize EBV and CMV viral antigens, and the tumor associated antigen, Wilms tumor 1||Cancer, autoimmune, and viral diseases||USA||San Francisco|
|Autolus Limited||Anti-GD2 chimeric antigen receptor (CAR)||Pediatric neuroblastoma||UK||White City|
|Bellicum Pharmaceuticals||CIDeCAR & GoCAR-T Technology||Hematological cancers and solid tumors||USA||Houston|
|bluebird bio||bb2121 (co-developed with Celgene)||Multiple myeloma||USA||Cambridge|
|Calibr||“Switchable” CAR-T cell that uses antibody-based switch molecules||Solid tumors and other cancers||USA||La Jolla|
|CARsgen Therapeutics||Anti-GPC3 CAR-T for hepatocellular carcinoma (HCC), anti-GPC3 CAR-T for squamous lung cancer (SLC), cancer-specific anti-EGFR CAR-T for glioblastoma multiforme (GBM) and anti-Claudin18.2-CAR-T for gastric and pancreatic cancer||Solid tumors and and hematology malignancies||China||Shanghai|
|Cartherics Pty Ltd||Mesoblast and Cartherics have partnered to produce allogeneic CAR-T cells from iPSCs||Solid cancers||Australia||Clayton|
|Celgene Corporation||bb2121 (co-developed with bluebird bio); Acquired Juno Therapeutics’ CAR-T assets for $9 billion in January 2018||Multiple myeloma||USA||Summit|
|Cell Design Labs (Acquired by Gilead Sciences)||Throttle™ (an “on/off” switch that allows the control of CAR T-cell activity using small molecules) and synNotch™ (a synthetic gene expression system||Various cancer targets||USA||Emeryville|
|Cellectis||UCART19 (being co-developed by Servier, Pfizer, & Cellectis)||Acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm||USA||New York|
|Celularity||Varied CAR-T assets; 200 issued or pending patents||Various Applications||USA||Warren Township|
|Celyad||Therapeutic Immunotherapy Using NKR-2 T cells (THINK)||Cancer applications||USA||New York|
|Fate Therapeutics||FT819||Solid tumors||USA||La Jolla|
|Fortress Bio||CD20-directed CAR T||Relapsed or refractory B-cell non-Hodgkin lymphomas||USA||New York|
|Gilead Sciences||eACT™ technology platform; Yescarta||Relapsed or refractory large B-cell lymphoma in adult patients||USA||Foster City|
|Humanigen, Inc.||Humaneered® platform||Rare hematologic cancers||USA||Burlingame|
|Immune Therapeutics||Chimeric Super Antigen Receptor T-Cell (CAR-T) Cocktail Therapy||Various Applications||USA||Orlando|
|Juno Therapeutics||JCAR015 (CD19-CAR T Cell Product Candidate in Phase 2)||Various cancer targets||USA||Seattle|
|JW Therapeutics||JWCAR029||B-cell malignancies||China||Shanghai|
|Kite Therapeutics||eACT™ technology platform; Yescarta||USA||El Segundo|
|Leucid Bio||Solid head and neck cancer||UK||London|
|Lion TCR Pte. Ltd.||CAR-T cell therapy licensed from Technical University of Munich||Viral-related cancer and chronic hepatitis B||Singapore||Singapore|
|Medisix Therapeutics Pte Ltd.||Exclusive licensing agreement with the National University of Singapore (NUS) for CAR-T technologies||T-cell lymphoma and leukemia||Singapore||Unknown|
|Mesoblast Ltd.||Mesoblast and Cartherics have partnered to produce allogeneic CAR-T cells from iPSCs||Solid cancers||Australia||Melbourne|
|Mustang Bio||MB-101 (IL13Rα2-specific CAR-T cells)||Hematologic malignancies and solid tumors||USA||New York|
|Nanjing Legend Biotech||LCAR-B38M (anti-BCMA CAR-T cell product)||Various liquid and solid tumors; Clinical trial underway for multiple myeloma||China||Jiangsu province|
|Novartis||Kymriah||B-cell acute lymphoblastic leukemia||Switzerland|
|Poseida Therapeutics||P-PSMA-101 (PSMA-specific stem cell memory CAR-T drug candidate)||Prostate Cancer||USA||San Diego|
|Precision BioSciences||ARCUS genome editing technology||Various targets||USA||Durham|
|Servier||UCART19 (being co-developed by Servier, Pfizer, & Cellectis)||Acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm||France||Neuilly-sur-Seine|
|Shire||ARCUS genome editing technology||Various targets||USA||Lexington|
|Sorrento Therapeutics (and Cellular Therapy Subsidiary, TNK Therapeutics, Inc.)||anti-CEA CAR-T||Liver Metastases||USA||San Diego|
|TC BioPharm||ImmuniCell® / gamma delta CAR T cells||Hematologic and solid tumor targets||UK||North Lanarkshire|
|Xyphos Inc.||convertibleCAR™ technology||Various targets||USA||San Francisco|
|Ziopharm||Sleeping Beauty (SB) platform||Recurrent glioblastomas||USA||Boston|
Future of CAR-T
At first the trend was subtle, but with two CAR-T approvals by the FDA in 2017 (Kymriah and Yescarta), the tide has swelled and created a craze for promising CAR-T product candidates.
As biotechnology companies rapidly advance cell therapy research that focuses on remedies for cancer, CAR-T represents a viable therapeutic strategy that harbors great potential.