AplaGen has discovered cytokine mimetic peptides which have extraordinary potential to improve prognosis and quality of life for patients with malignant diseases. AplaGen´s strategy is focusing on further development of these tracks in hematologic and oncologic indications until advanced clinical stage. The two products are peptide-mimics of erythropoietin and of thrombopoietin, two glycoprotein hormones, which are needed to produce red blood cells (erythropoietin) and blood platelets (thrombopoietin). Both products were designed to be even more specific than their natural precursors and/or to overcome limitations which are associated withrec. versions of the natural cytokines. Both products are small, fully synthetic peptides, which are conjugated to the inert biopolymer hydroxyethylstarch (HES).

AplaGen has made breakthrough discoveries in this field and offers third parties to design improved peptides with novel patentable properties and/or to implement strategies to conjugate protein or peptide products to HES. Such Innovation Partnerships are offered at competitive conditions and make use of the proven capability of AplalGen´s team.

SESTide (HemoMer^®)  -  EPO Mimetic Peptide (EMP)

SESTide combines EPO mimetic peptides with hydroxyethylstarch as carrier. While the peptides are highly specific for the homodimeric EPO receptor, the starch is improving their pharmacokinetic properties. The conjugation strategy to HES does not only improve the pharmacokinetic properties of the peptides, but is also improving their potency. This feature is not seen with other carriers (e.g. PEG) which are used to increase molecular weights of protein or peptide drugs. In general, SESTide can be used in the same indications as recombinant EPOs today:

Recombinant EPO is used as a biopharmaceutical drug in patients with anaemia caused by:

• cancer (treatment-related anaemia)
• renal dysfunction (related to dialysis), and
• chronic kidney disease

With SESTide AplaGen has developed an innovative, patent protected product for the EPO-market. SESTide is a long-lasting fully synthetic EPO-mimetic peptide and will be competitive to new generation erythropoietin-receptor stimulating agents (ESAs; long-lasting erythropoietins and peptides). It shows best-of-(peptide)class properties in vivo and can be manufactured at very low cost. SESTide is not able to induce antibodies to endogenous EPO of the patient (i.e. to induce PRCA); it is a potential treatment option for such patients with autoantibodies to endogenous EPO. We expect the limitations, which are actually associated with the use of EPO in cancer patients, not to be valid for SESTide. Its positioning in the market will further be based on the excellent control of therapy due to fully biodegradable HES (Hydroxyethylstarch) as carrier molecule. The renal indications for this drug are open to licensing, while AplaGen will focus on the hematologic and oncologic indications.  [Contact...]

ThromboMer^®  (Thrombopoietin Mimetic Peptide (TMP))

Thrombomer combines TMP with hydroxyethylstarch as carrier. This product shares is highly synergistic with SESTide. Similar to SESTide, it will be developed primarily in oncologic indications, while other indications are  open to licensing for interested parties.

Thrombopoietin is a cytokine which is closely related to erythropoietin (see above). However, thrombopoietin is not produced in the kidney but in the liver and a potent stimulator of blood platelet formation in the bone marrow. It is thus responsible for another important pathway of differentiation of blood cells. Blood platelets are part of the coagulation system and are responsible for both, bleeding control and coagulation. If platelet counts are too low, this can cause severe internal bleeding.

Major diseases causing low platelets counts (i.e. thrombocytopenia or thrombopenia) are:

• Cancer and cytostatic (bone marrow depressive) treatment regimens for cancer
• Hematologic diseases such as myelodysplastic syndrome, leukemia, with associated thrombocytopenia
• Auto-Immune diseases (e.g. idiopathic thrombocytopenic purpura (ITP))
• Severe chronic liver disease

Lead Optimisation is in progress and proof of principle in vitro was achieved. Due to high synergies with the SESTide project, this project will close up over time to the project on erythropoietin mimetic peptides.