• Investigational BKX-001 is an oral small-molecule activator of BAX, developed as a potential treatment for leukemia, lymphoma and solid tumors1.
• Ipsen obtains an exclusive license to research, develop, manufacture and commercialize novel therapeutics targeted to the BCL-2 associated protein (BAX), an effector of apoptosis.
• Ipsen and BAKX Therapeutics Inc. will be jointly responsible for research and development activities and will jointly share in the profits from commercialization.
Ipsen and BAKX Therapeutics, Inc. (have signed an exclusive worldwide-collaboration agreement to research, develop, manufacture and commercialize BKX-001 as a potential treatment for leukemia, lymphoma and solid tumors.
Apoptosis is the naturally occurring process of programmed cell death. Deregulated apoptosis can lead to uncontrolled cell division and the development of a tumor.2 The apoptosis cell-signaling pathway has been proven to be a target for cancer therapy with the development and approval of BCL-2 inhibitors for the treatment of certain hematological malignancies.3 BAX is a novel target in this pathway that is downstream of all anti-apoptotic proteins like BCL-2, BCL-XL, MCL-1 etc.4 Direct activation of BAX has several possible outcomes as an investigational cancer therapy, potentially addressing multiple tumor types and the resistance encountered while targeting only the antiapoptotic BCL-2 family proteins. BAX activation by small-molecule agonists have been shown to promote apoptosis in leukemia-cell lines and human samples, while sparing healthy cells in vitro and suppress human acute myeloid leukemia xenografts and increased host survival without toxicity in vivo.5
Dr. Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen, said “As part of our strategy, we continue to strengthen our pipeline and deliver exciting external-innovation opportunities. We are, therefore, delighted to partner with the expert team at BAKX Therapeutics to move BKX-001 into further preclinical development, with the goal of achieving a development candidate that can be evaluated for the potential treatment of hematological malignancies and solid tumors. Importantly, this collaboration also reflects the shared values across our two organizations and, as a result, we will be building a strong cross-company team to advance this innovation for people living with these forms of cancer, and their healthcare teams.”
Sree Kant, Founder and CEO of BAKX Therapeutics Inc. said “We are excited to partner with Ipsen on investigational BKX-001. This program is the result of pioneering work on the BAX protein driven by our scientific co-founders Loren D Walensky and Evripidis Gavathiotis. This partnership brings together Ipsen’s excellent clinical development and commercial capabilities with our industry-leading knowledge of the BAX protein and our unique computational platform. This is a collaboration of very distinct complementary capabilities that can together drive important treatment options in cancer therapy for patients, faster.”
Under the agreement, Ipsen will pay BAKX Therapeutics Inc. $14.5m upon closing, comprising an equity investment and an upfront payment, followed by up to $837.5m in milestone payments. The companies would also share equally costs and profits.
BKX-001 is an oral small molecule activator of the BCL-2 associated protein-X (BAX). BKX-001 binds to the trigger site of BAX in a catalytic manner, stimulating a conformational change in BAXto drive apoptosis in tumor cells. BKX-001 is active in hematological malignancies including various leukemias and lymphomas and select solid tumors with high unmet need.BKX-001combinations with BCL-2family inhibitors have shown a strong synergistic effect suggesting an approach for treating resistant tumors. Rational biomarker-driven combination approaches with other anti-cancer agents are also under evaluation.
Ipsen (ipsen.com) is a global, mid-sized bio pharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience; it also has a well-established Consumer Healthcare business. With Total Sales of over €2.5bn in FY 2020, Ipsen sells more than 20 medicines in over 115 countries, with a direct commercial presence in more than 30 countries. The Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has c.5,700 colleagues worldwide.
About BAKX Therapeutics
BAKX Therapeutics (bakxtx.com) is a NY & Boston based biotech company focused on targeting the mitochondrial apoptosis pathways. BAKX was co-founded by world leading researchers in the field of apoptosis and computationally aided drug discovery. BAKX’s integrated platform is characterized by (i) unique target and pathway knowledge, combined with (ii) deep expertise in working with conformationally dynamic protein interactions, and(iii) pioneering computational methodologies for simulating protein interactions in the membrane. BAKX’s leading asset BKX-001 (partnered with Ipsen) is focused on targeting the BAX protein. In addition, the BAKX platform is deployed towards drugging two other undisclosed apoptosis targets implicated in various solid tumors and the build up of resistance.
1. BAKX Therapeutics. The apoptosis company. Pipeline. bakxtx.com/pipeline/ (last accessed July 2021).
2. National Human Genome Research Institute. genome.gov/genetics-glossary/apoptosis (last accessed July 2021).
3. Venclyxto SmPC. European Medicines Agency. Available here: ema.europa.eu/en/medicines/human/EPAR/venclyxto
4. A.R.D. Delbridge and A. Strasser Cell Death Differ., 22 (2015), pp. 1071-1080. Available here: nature.com/articles/cdd201550.
5. D.E. Reyna, T.P. Garner, A. Lopez, F. Kopp, G.S. Choudhary, A. Sridharan, S.R. Narayanagari, K. Mitchell, B. Dong, B.A. Bartholdy et al. Cancer Cell, 32 (2017), pp. 490-505. Available here: cell.com/cancer-cell/fulltext/S1535-6108(17)30364-1