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Collaboration Between Magenta Therapeutics and Heidelberg Pharma Expands Application of ATAC Technology

Published on 05th March

Magenta Therapeutics, a company developing therapeutics to improve and extend the use of curative bone marrow transplants, and Heidelberg Pharma, developing new options to address major challenges in cancer therapy, have signed an exclusive multi-target research agreement.

The collaboration combines Magenta’s stem cell platform with proprietary antibodies across up to four exclusive targets with Heidelberg Pharma’s proprietary ATAC (Antibody Targeted Amanitin Conjugates) platform.

Unmet medical need
Healthy bone marrow stem cells and the blood cells they create are crucial for survival, but certain diseases can affect the bone marrow, interfering with its ability to function properly. A bone marrow transplant is a process to replace unhealthy bone marrow with healthy bone marrow stem cells. Bone marrow transplant can save the lives of patients with blood cancers and genetic diseases and is a potential cure for patients with severe refractory autoimmune diseases.

Photo 1.0: Prof. Dr. Andreas Pahl Chief, Scientific Officer of Wilex and Heidelberg Pharma.

However, the high risks, toxic side effects and complexity of the procedure currently prevent many patients from being able to benefit.

Magenta is working to address these challenges through its integrated portfolio of therapeutics.

Meeting the need
“There is a significant need for targeted conditioning regimens for bone marrow transplant, and this is a key area of focus for Magenta,” said Michael Cooke, Ph.D., Chief Scientific Officer, Magenta Therapeutics.

“Our partnership with Heidelberg Pharma is an important step in our development of proprietary targeted antibody drug conjugates for conditioning,” he added.

“Amanitin is one of the promising toxins we are exploring in our targeted conditioning programs, and our partnership with Heidelberg Pharma will allow us to fully evaluate the potential of this payload,” Cooke added.

Image 1.0: Chemical structure of the amatoxin alpha-amanitin

“We are delighted to collaborate with Magenta Therapeutics, a company at the forefront of transforming the field of bone marrow transplant medicine.

We believe this partnership further validates our technology and underscores our leadership in the field of Antibody Targeted Amanitin Conjugates, a new mode of action for attacking cancer,” noted Andreas Pahl, Ph.D., Chief Scientific Officer, Heidelberg Pharma.

“We look forward to working with Magenta to expand the application of our ATAC technology to new targets to potentially address unmet needs in bone marrow transplantation,” he concluded.

Heidelberg’s proprietary Antibody Targeted Amanitin Conjugate (ATAC) technology includes amatoxins,small bicyclic peptides (bicyclic octapeptides) naturally occurring in the death cap mushroom (aminita phalloides). Around the world, this mushroom is best known for causing most cases of fatal mushroom poisonings.*

The unique compound is a potent and selective inhibitor of RNA polymerase II, a vital enzyme in the synthesis of mRNA, a mechanism that is crucial for the survival of eukaryotic cells, and small nuclear RNA (snRNA). Without mRNA, essential protein synthesis and cell metabolism grind to a halt leading to cell death.

Symptomatically, amatoxins cause necrosis of the liver, also partly in the kidney, with the cellular changes causing the fragmentation and segregation of all nuclear components. [1]

Pre-clinical studies
In pre-clinical testing, ATACs have shown potential advances and be highly efficacious, overcoming frequently encountered resistance mechanisms and combating even quiescent tumor cells.  These advances include higher solubility and uniformity due to greater hydrophilicity than other cytotoxic payloads. This, in turn, could further advance the development of novel therapeutic, including neoovel antibody-drug conjugates and other targeted agents.

Multi-target research agreement
Under the terms of the multi-target research agreement, Magenta will have access to Heidelberg Pharma’s Amanitin toxin-linker platform technology. Magenta has an option for an exclusive target-specific license for global development and commercialization rights to each of the product candidates resulting from the research collaboration.

Heidelberg Pharma will receive upfront technology access and exclusivity fees and payments for research support. As part of the agreement between the companies, Heidelberg Pharma is eligible to receive option fees, clinical development, regulatory and sales-related milestone payments up to US $334 million, if Magenta exercises all target options and all milestones are met.

In June 2017 Heidelberg Pharma, also signed an multi-target research agreement with Takeda Pharmaceutical Company for the joint development of antibody-drug conjugates that use amanitin as the payload.

* The lethal dose for humans is estimated at about 0.1mg/kg body weight (approximately 8mg for an 80kg person).

Last editorial review: March 5, 2018

Featured Image: Contracts being signed. Courtesy: © 2017. Fotolia. Used with permission. Image 1.0: Chemical structure of the amatoxin alpha-amanitin. Courtesy: © 2017 Edgar181, Public domain via Wikimedia Commons. Photo 1.0. Prof. Dr. Andreas Pahl Chief, Scientific Officer of Wilex and Heidelberg Pharma. Courtesey: Heidelberg Pharma. Used with permission.

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