Interim Phase IIa Results for Spiegelmer® Olaptesed Pegol (NOX-A12) in CLL and MM Studies

Five posters on NOXXON compound at 2013 American Society of Hematology (ASH) conference

(PresseBox) ( Berlin, )
NOXXON Pharma disclosed interim data from two independent clinical phase IIa studies of the anti-CXCL12/SDF-1 Spiegelmer® olaptesed pegol (NOX-A12) at the 55th annual meeting of the American Society of Hematology (ASH) in New Orleans, LA, USA from 7-10 December 2013.

In the first study, olaptesed was administered to relapsed chronic lymphocytic leukemia (CLL) patients in combination with bendamustine and rituximab. In the second study, olaptesed was combined with bortezomib and dexamethasone in patients with relapsed multiple myeloma (MM). Data from the 9 patient pilot groups in each study were presented.

In the trial focusing on relapsed CLL, olaptesed treatment resulted in an effective and prolonged mobilization of CLL cells into the peripheral blood. This mobilization reflects olaptesed's ability to block tumor-microenvironment interactions, which is thought to increase tumor cell sensitivity to killing by chemotherapeutic agents. In addition, the 100% overall response rate (ORR) and 22% complete response (CR) rate as well as the virtual absence of additional toxicity on top of the treatment with bendamustine and rituximab (BR) observed in this pilot group compares very favorably with historical controls. Provided that this promising clinical picture is maintained in the total sample of 33 patients, NOXXON plans to further develop this novel anti-CXCL12/SDF-1 Spiegelmer®.

In patients with relapsed MM, anti-CXCL12/SDF-1 Spiegelmer® olaptesed showed the same effect of mobilization of plasma cells into the peripheral blood. In addition, an overall response rate (ORR) of 67% including 22% very good partial responses (vgPR) was achieved in this pilot group. Importantly, treatment with olaptesed was not associated with additional toxicity on top of Velcade®/bortezomib and dexamethasone (VD). If these preliminary results can be maintained in the total sample of 28 patients, then again further development of this novel anti-CXCL12/SDF-1 Spiegelmer® will be warranted.

The titles and contributors for the two above mentioned poster presentations at ASH are as follows:

- Saturday, December 7, 5:30 PM - 7:30 PM, Hall E; Session 642, Publication number: 1635

Anti-CXCL12/SDF-1 Spiegelmer® NOX-A12 Alone and In Combination With Bendamustine and Rituximab In Patients With Relapsed Chronic Lymphocytic Leukemia (CLL): Results From A Phase IIa Study Marco Gobbi, Michael Steurer, Federico Caligaris-Cappio, Marco Montillo, Ann Janssens, Livio Trentin, Thomas Dümmler, Stefan Zöllner, Stefan Zeitler, Kai Riecke, Anna Kruschinski

- Saturday, December 7, 5:30 PM - 7:30 PM, Hall G, Session 653, Publication number: 1951

Anti-CXCL12/SDF-1 Spiegelmer® NOX-A12 Alone and In Combination with Bortezomib and Dexamethasone In Patients With Relapsed Multiple Myeloma: Results From A Phase IIa Study Heinz Ludwig, Katja Weisel, Monika Engelhardt, Richard Greil, Anna Maria Cafro, Maria Teresa Petrucci, Thomas Dümmler, Stefan Zöllner, Stefan Zeitler, Kai Riecke, Anna Kruschinski Three more poster presentations at ASH have the following titles and contributors:

- Sunday, December 8, 6:30 PM - 8:30 PM, Hall E, Session 506, Publication Number: 2454

SDF-1 Inhibition Using Spiegelmer® NOX-A12 as a Novel Strategy for Targeting AML Cells Within their BM Microenvironment Rodrigo Jacamo, Zhihong Zeng, Ye Chen, Yuexi Shi, Teresa McQueen, Anna Kruschinski, Marina Konopleva, Peter P. Ruvolo, Michael Andreeff

- Monday, December 9, 6:00 PM - 8:00 PM, Hall E, Session 604, Publication Number: 3851

Targeting the Protective Microenvironment in Multiple Myeloma (MM): An Analysis of The CXCL12/CXCR4-Axis and its Inhibitors AMD3100 and NOX-A12 Combined with Antimyeloma Substances, Such As Pomalidomide and Carfilzomib Anna Simon, Dagmar Wider, Marie Follo, Johannes Waldschmidt, Martina Kleber, Ralph Waesch, Monika Engelhardt

- Monday, December 9, 6:00 PM - 8:00 PM, Hall E, Session 641, Publication Number: 4111

The Spiegelmer® NOX-A12 Abrogates Homing of Human CLL Cells To Bone Marrow and Mobilizes Murine CLL Cells in the E1 Transgenic Mouse Model Of CLL Elisabeth Hinterseer, Tamara Girbl, Evelyn Hutterer, Petra Berghammer, Sylvia Ganghammer, Eveline Sifft, Josefina Pinon Hofbauer, Alexander Egle, Anna Kruschinski, Richard Greil, Tanja Nicole Hartmann

Members of NOXXON's drug development team and collaboration partners will be at the ASH conference to explain the mode of action and clinical potential of this innovative drug candidate.

About olaptesed pegol (NOX-A12)

Olaptesed specifically binds and neutralizes CXCL12/SDF-1 (CXC chemokine ligand 12/Stromal Cell-Derived Factor-1), a chemokine which activates and attracts immune and non-immune cells including stem cells from the bone marrow. CXCL12 binds with high affinity to two chemokine receptors, CXCR4 and CXCR7. The CXCL12/CXCR4/CXCR7 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis. Inhibition of CXCL12 binding to its receptors disrupts tumor-microenvironment interactions thereby sensitizing tumor cells to therapy as well as preventing invasion and metastasis in some solid tumors. This suggests that olaptesed in combination therapies could be beneficial in the treatment of various hemtological and solid malignancies.

Indeed, olaptesed has shown promising activity in models of both hematological and solid tumors in addition to models of stem cell mobilization. NOXXON's collaborators have shown that in multiple myeloma models olaptesed detached myeloma cells from stromal cells and sensitized them to killing by Velcade®/bortezomib both in vitro and in vivo1. Olaptesed has also been shown to inhibit chemotaxis of patient-derived primary CLL cells towards higher concentrations of CXCL12 and to have distinct properties from CXCR4 antagonists2. In an animal model of glioblastoma, olaptesed treatment resulted in a significant extension of lifespan of animals when used in combination with radiation therapy3.

In Phase I studies with healthy volunteers, single doses of olaptesed up to 10.8 mg/kg and daily doses up to 2 mg/kg for five days were found to be safe and well tolerated and resulted in dose-dependent mobilization of white blood cells and CD34+ hematopoietic stem cells as predicted by preclinical studies.

NOXXON received grant support within the program "KMU-innovativ" from the German Federal Ministry of Education and Research (BMBF) for the preclinical and early clinical development of olaptesed.

Further information about the ongoing olaptesed Phase IIa clinical trials is available at ClinicalTrials.gov: relapsed MM (ID: NCT01521533) and relapsed CLL (ID: NCT01486797).

1 Roccaro AM (2011) ASH 53rd Annual Meeting, oral presentation 887, Session 652
2 Hoellenriegel J & Zboralski D, et al., Blood 2013 Nov 25.
3 Liu S-C et al., Neuro Oncol 2013 (in press)
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