On May 4, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, led by its Orascovery platform, reported that it has acquired Kuur Therapeutics, Inc., the leading developer of off-the-shelf CAR-NKT cell immunotherapies for the treatment of solid and hematological malignancies (Press release, Athenex, MAY 4, 2021, View Source [SID1234579065]).
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"We are excited to add Kuur Therapeutics and its innovative allogeneic CAR-NKT technology to the Athenex platform," said Dr. Johnson Lau, Chief Executive Officer of Athenex. "Kuur’s innovative technology, combined with our TCR program, could propel us into a leadership position in cell therapy. This platform also has the potential to provide synergies with other assets in our pipeline."
Dr. Dan Lang, President of Athenex Cell Therapy, added, "We are thrilled to combine our TCR program with the groundbreaking NKT cell platform developed by Professor Leonid Metelitsa at Baylor College of Medicine and Texas Children’s Hospital. We are confident that we can continue to innovate on the NKT cell platform with Dr. Metelitsa to provide a solution that may address some of the known limitations associated with the first generation of cell therapy treatments focused on autologous CAR-T. We aspire to convert cancer into a chronic disease."
Under the terms of the agreement, Athenex will pay $70 million upfront to Kuur shareholders and certain of its former employees and directors, comprised primarily of equity in Athenex common stock. Additionally, they are eligible to receive up to $115 million of milestone payments, which may be paid, at Athenex’s sole discretion, in either cash or additional Athenex common stock (or a combination of both).
Kevin S. Boyle, Sr., Chief Executive Officer of Kuur, stated, "CAR-NKT cells offer a distinct set of advantages over other immune effector cells commonly used for cell therapy. We are excited that the leadership at Athenex recognizes the significant potential of this approach to provide effective treatment options for patients with both solid and hematological tumors. The development of these innovative therapies will be accelerated by combining Kuur’s experienced team with the extensive resources of Athenex."
About the CAR-NKT Platform and Pipeline
Natural killer T (NKT) cells are innate-like T lymphocytes that express a semi-invariant TCR and preferentially reside in and traffic to tissues, including the liver and bone marrow. Evidence suggests that NKT cells do not mediate graft-versus-host-disease (GvHD) making them an ideal candidate for off-the-shelf CAR therapy. In addition to this differentiated cellular biology, the CAR constructs are engineered to:
Secrete IL-15 to improve their activation, persistence and anti-tumor activity
Down-regulate human leukocyte antigen (HLA) class I and II to diminish their alloreactivity and improve persistence in allogeneic recipients
As described in Kuur’s January 2021 press release, the GINAKIT2 clinical trial is a phase I study of KUR-501, an autologous CAR-NKT cell product, targeting GD2 in patients with relapsed/refractory (R/R) high risk neuroblastoma conducted at Baylor College of Medicine (BCM) and Texas Children’s Hospital.
Out of 10 evaluable patients, one complete response (CR) and one partial response (PR) have been observed to date, with stable disease (SD) in three additional patients. Tumor biopsy shows CAR-NKT cells homing to the neuroblastoma tumor site at all dose levels, which is an important biological property of NKT cells. KUR-501 has so far demonstrated a promising safety profile, with only one case of grade two cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS).
Additional data on the GINAKIT2 phase I study will be presented at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 24th Annual Meeting on May 14, 2021.
The ANCHOR clinical trial is an ongoing phase I study of KUR-502, an allogeneic (off-the-shelf) CAR-NKT cell product, targeting CD19 in adult patients with relapsed/refractory lymphoma and leukemia conducted at BCM.
Out of two evaluable patients, one CR and one PR have been observed to date at the lowest dose level of 1×107 cells/m2. One patient was initially observed to be a PR four weeks after infusion, but subsequently converted to a CR without additional therapy 12 weeks later. Biopsy of the patient’s lymph node at five weeks after infusion, prior to conversion to CR status, revealed viable, allogeneic CD19 CAR-NKT cells. The patient with the PR had previously failed autologous CAR-T cell therapy. KUR-502 has so far demonstrated a promising safety profile with no CRS, no ICANS, and no evidence of GvHD.
In 2016, Kuur Therapeutics and BCM signed an exclusive licensing and co-development agreement around cellular immunotherapy products for the treatment of cancer. The co-development collaboration has been instrumental in advancing KUR-501 and KUR-502 into the clinic, and in advancing KUR-503 into IND-enabling preclinical studies. The collaboration accelerated the pioneering work of Dr. Leonid Metelitsa, Professor of Pediatrics – Oncology at BCM and Texas Children’s Hospital. Dr. Metelitsa and his team have shown the potential therapeutic advantages of functionally enhanced CAR-modified NKT cells. Dr. Metelitsa’s research team is part of Texas Children’s Cancer Center and the Center for Cell and Gene Therapy (CAGT) at BCM, Texas Children’s Hospital and Houston Methodist Hospital. The CAGT has more than 20 years of experience working with genetically modified immune cells for the treatment of cancer and has conducted more than 40 clinical studies investigating cellular immunotherapies for the treatment of cancer.
Cooley (UK) LLP is acting as the sole advisor to Athenex, Inc. and SVB Leerink is acting as financial advisor with HMB Legal Counsel acting as legal advisor to Kuur Therapeutics in connection with the transaction.
About KUR-501
KUR-501 is an autologous product in which NKT cells are engineered with a CAR targeting GD2, which is expressed on almost all neuroblastoma tumors, as well as other malignancies. KUR-501 is being tested in the phase 1 GINAKIT2 clinical study (NCT03294954) in patients with R/R high risk neuroblastoma. The single-arm study will evaluate six dose levels of KUR-501 with patients receiving pre-dose lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine.
Neuroblastoma is a pediatric cancer and patients with R/R high risk neuroblastoma have a poor prognosis and a significant unmet medical need. The KUR-501 development program is also designed to provide autologous proof-of-concept for CAR-NKT cells in solid tumors using a validated target.
The GINAKIT2 study is supported by Kuur Therapeutics and Alex’s Lemonade Stand Foundation, conducted by Kuur’s collaborator, BCM, and is currently recruiting patients.
About KUR-502
KUR-502 is an allogeneic product in which NKT cells are engineered with a CAR targeting CD19. KUR-502 is built on Kuur’s next-generation CAR-NKT platform with novel engineering capabilities that harness and enhance the unique properties of NKT cells. The NKT cells used in Kuur’s CAR-NKT platform have a semi-invariant TCR that does not distinguish between self- and non-self-tissues, making the cells unlikely to induce GvHD when given to another person.
The ANCHOR clinical study (NCT03774654) is a phase 1, first-in-human, dose escalation evaluation of KUR-502 in adults with R/R CD19 positive malignancies including B cell lymphomas, acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) The single-arm study will evaluate three dose levels with patients receiving lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by infusion with KUR-502.
Patients with R/R CD19-positive malignancies have limited effective treatment options. While CD19-directed autologous CAR-T cells are now available for these patients, they are limited by a requirement for patient leukapheresis, delays to receive treatment due to the requirement for autologous manufacturing, and variable final product quality. Off-the-shelf KUR-502 is designed to overcome these limitations.
The ANCHOR study is being sponsored and conducted by Kuur’s collaborator, BCM and is currently recruiting patients.
About KUR-503
KUR-503 is an allogeneic product under development in the laboratory of Dr. Andras Heczey, Assistant Professor of Pediatrics in the Section of Hematology-Oncology at BCM and Texas Children’s Hospital. KUR-503 is unique product, in which NKT cells are engineered with a CAR targeting GPC3 (glypican-3) and like all of Kuur’s allogeneic products, is built on Kuur’s next-generation CAR-NKT platform. GPC3 is a molecule that is highly expressed on most hepatocellular carcinomas (HCC), but not normal liver or other non-neoplastic tissue, making it an ideal target. Because NKT cells traffic to the liver, prevent the formation of new HCC, and their presence in HCC is associated with better outcomes, this platform is an excellent vehicle for delivery of immune effector therapy for patients with HCC. HCC is now the fourth most common cause of cancer related death worldwide, with an estimated 750,000 new cases each year. Although there have been some recent approvals of new agents to treat advanced HCC, these patients still have poor outcomes and there is a significant unmet need.
KUR-503 is currently in preclinical development and the company is planning to initiate a first in human phase 1 clinical trial in 1H 2022.