Through 20 years of careful experimentation and optimization, we’ve created Trilytes for the future.
KOSMAS has developed a proprietary technology for the treatment of leukemias that is also suited for other applications, from hematologic malignancies to solid tumors and chronic inflammatory diseases. Our approach is based on principles
of antibody affinity for tumor antigens, the cooperative effects of spectral targeting, selectivity, and a judicious choice of target pairs on cancer stem cells. Trilytes integrating these components will become a pillar of
future cancer therapy.
Our prototype Trilyte, the clinical candidate KT1, is designed for dual-targeting of leukemic stem cells and bulk malignant cells in patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). The technological
advance of KT1 lies in its capability for dual-targeting, which results in enhanced selectivity and stronger lysis of leukemic cells, combined with fewer harmful “on target, off tumor” side effects. KT1’s third binding head connects
Natural Killer (NK) cells to leukemic cells with great binding strength and activates them for target cell lysis with high efficacy, combined with the favorable safety profile of NK cells. KT1’s smaller size allows for better tissue
penetration, and its prolonged retention on the target cell surface leads to more efficient killing.
Continue reading below to learn more about our Trilytes.
The Wide World of Trilytes
Effective against a broad range of AML subtypes.
Trilytes are effective against an unusually broad range of AML subtypes. This happens because the genetic mechanisms that make different subtypes resistant to chemotherapy, do not make them resistant to killing by Trilytes plus NK cells.
Reside on target cells longer and better engage killer cells.
Single-targeting agents are rapidly internalized from the cell surface after binding their targets and rendered inaccessible to killer cells. Trilytes bind two different targets on the same cell, which strongly reduces internalization. They remain longer on the cell surface, leading to more effective engagement of killers and cancer cell lysis.
Reduced probability for outgrowth of resistant variants.
Under treatment with mono-targeting therapies, cancer cell variants often grow out, which have become resistant via loss of the target. The probability for outgrowth of double-escaping variants through loss of both targets is greatly reduced. Trilytes still function, even when one of the targets is lost.
Increased selectivity of lysis.
In concert with NK cells, dual-targeting Trilytes preferentially kill cancer cells expressing both targets at high surface density over related cells expressing both at lower density. A combination treatment with two corresponding mono-targeting agents (e.g. antibodies, diabodies), plus NK cells does not achieve this degree of selectivity.
High selectivity helps Trilytes to reach Leukemia Stem Cells (LSCs) and kill them, even when only as a few as 1:100,000 AML cells may be AML-LSCs. High selectivity is uniquely achieved through our new molecular format combined with our choice of a highly suited pair of target antigens, which are present in far greater density on the surface of AML-LSCs than on the bulk leukemic blasts and corresponding normal blood cells.
Fewer harmful side-effects.
Normal cells of some blood cell families and their precursors also carry one or both of the antigens targeted by KT1, however in lower surface density than on most AML blasts and AML-LSCs. These normal cells can also be lysed by KT1 plus NK cells, but greater doses of KT1 are needed for equal lysis.
Owed to its enhanced cytolytic activity for antigen double-positive target cells achieved by dual-targeting, KT1 will likely be used in clinical applications in far lower doses than existing mono-targeting agents. At these lower doses, KT1 will likely cause fewer harmful side effects, so-called “on target, off tumor” haemato-toxicities than competing agents.
Trilytes engaging NK cells have a favorable safety profile.
The patent-protected platform technology allows the design of Trilytes engaging a killer cell of choice, optimally matched to the cancer at hand. For the design of KT1, NK cells were chosen because they are the human body’s sentinels and first-line of defense against spontaneously arising AML cells.
The therapeutic molecules and cells of our competitors often engage T lymphocytes as killers because of their stronger cytolytic potential. However, killing by T cells is accompanied by the release of a more toxic cocktail of inflammatory mediators than the engagement of NK cells. KOSMAS proposes that the limiting factor for successful AML therapy is not primarily the cytolytic power of the killer cells, but the limiting selectivity of existing agents, which do no discriminate well enough between malignant and normal cells.
KOSMAS improves this discrimination with the radically new concept of “dual-targeting” and expects that NK cells as nature’s own weapon against AML, will be potent enough in concert with Trilytes to achieve the needed break-through in the treatment of AML.
Trilytes will penetrate tissues better.
Trilytes have half the mass of therapeutic antibodies and can better penetrate tumor masses. We expect them to be able to reach leukemia stem cells in their bone marrow niches better than antibodies. However, they are large enough to escape excretion on first passage through the kidneys, which endows them with a sufficient plasma half-life for leukemia therapy. The size of KT1 has been optimized over the needs for a sufficient plasma half-life, a rapid distribution over the human body and a particularly fast and effective NK cell-mediated killing.