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OUR PROGRAMS

we are developing fusion protein therapeutics for the treatment of cancer.

Our fusion protein approach tethers a tumor-targeting antibody fragment to a protein cytotoxic payload to form a single protein molecule designed to selectively and broadly kill cancer cells while minimizing toxicity to healthy cells and to activate the body’s innate immune response system.

EpCAM is expressed in many cancers, and we believe there is potential for Vicinium to address a broad range of solid tumors.
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PIPELINE

Our fusion protein approach tethers a tumor-targeting antibody fragment to a protein cytotoxic payload to form a single protein molecule designed to selectively and broadly kill cancer cells while minimizing toxicity to healthy cells and to activate the body’s innate immune response system. We are initially focused on the treatment of non-muscle invasive bladder cancer (NMIBC).

VICINIUM FOR BLADDER CANCER

our initial focus for vicinium is on treating bladder cancer.

Vicinium is being evaluated in the Phase 3 VISTA trial for the treatment of patients with non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG), which is the current standard of care for NMIBC. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can no longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

VISTA TRIAL FOR NMIBC

preliminary VISTA Trial results

The VISTA Trial completed enrollment in March 2018. In January 2019, we announced preliminary data from the 6-month, 9-month and 12-month time points, as well as updated 3-month data from all Carcinoma in situ patients enrolled in the clinical trial. The preliminary findings are highly encouraging, demonstrating that treatment with Vicinium results in clinically meaningful efficacy and favorable safety and tolerability. In addition, the data are consistent with the results of Vicinium in our completed Phase 1 and Phase 2 clinical trials. Complete, 12-month data from all patients in the trial are expected to be reported in mid-2019.

VICINIUM FOR HEAD & NECK CANCER

potential for treating additional cancers

We also believe Vicinium may have the potential to treat additional cancers, including squamous cell carcinoma of the head and neck (SCCHN). We have completed Phase 1 trials for an injectable form of Vicinium for the treatment of SCCHN that have demonstrated anti-tumor activity and safety. Data from these trials also demonstrated that certain patients who were injected with Vicinium in one tumor had responses in non-injected tumors as well, suggesting that Vicinium may promote an anti-tumor immune response and combine well with immunotherapies. In addition to the Phase 1 trials, we completed a Phase 2 trial in the United States, which demonstrated a reduction in the bidirectional size of the principle targeted tumor observed in 71 percent (10/14) of patients evaluated in the study.

VICINIUM COMBINATION POTENTIAL

We believe there is strong scientific rationale for Vicinium in combination with checkpoint inhibitors to treat a variety of cancers. Vicinium in combination with AstraZeneca’s anti-PD-L1, Imfinzi (durvalumab), is being evaluated in a Phase 1 study that is being run by the National Cancer Institute. The study is assessing safety and tolerability, as well as complete response rate and duratation of response as the key efficacy endpoints. We expect data from this study to guide additional combination potential and future trials.

RESEARCH PROGRAMS

We are exploring opportunities utilizing a next-generation payload called deBouganin (VB6-845d). This highly potent plant toxin is engineered to be de-immunized for systemic delivery, with a safety profile that we believe will provide a broad therapeutic window.

Publications

VB4-845 | Vicinium

R Dickstein, N Wu, B Cowan, C Dunshee, M Franks, F Wolk, L Belkoff, S Castellucci, J Holzbeierlein, G Kulkarni, A Weizer, D Lamm, S Ali, J Epstein, GP Adams, H Youssoufian, W Kassouf. VISTA, Phase 3 Trial of Vicinium, an EpCAM-Targeted Pseudomonas Exotoxin, in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer. Global Congress on Bladder Cancer 2018, September 20-21, 2018; Madrid, Spain

R.L. Dillon, S. Chooniedass, A. Premsukh, G.C. MacDonald, J. Cizeau and G.P. Adams. VB4-845 tumor cell killing in a combination with the anti-PD1, Nivolumab (poster). 2017 American Association for Cancer Research, April 1-5; Washington D.C.

Kowalski M, Guindon J, Brazas L, Moore C, Entwistle J, Cizeau J, Jewett MA, MacDonald GC. A Phase II Study of Oportuzumab Monatox: An Immunotoxin Therapy for Patients with Noninvasive Urothelial Carcinoma in situ Previously Treated with Bacillus Calmette-Guérin. J Urol. 2012 Nov; 188(5):1712-8. doi: 10.1016/j.juro.2012.07.020. Epub 2012 Sep 19.

Premsukh A, Lavoie JM, Cizeau J, Entwistle J, MacDonald GC. Development of a GMP Phase III Purification Process for VB4-845, an Immunotoxin Expressed in E. coli using High Cell Density FermentationProtein Expr Purif. 2011 Jul;78 (1):27-37. doi: 10.1016/j.pep.2011.03.009. Epub 2011 Mar 21.

Kowalski M, Entwistle J, Cizeau J, Niforos D, Loewen S, Chapman W, MacDonald GC. A Phase I Study of an Intravesically Administered Immunotoxin Targeting EpCAM for the Treatment of Nonmuscle-Invasive Bladder Cancer in BCG-Refractory and BCG-Intolerant Patients. Drug Des Devel Ther. 2010 Nov 15; 4:313-20. doi: 10.2147/DDDT.S14071.

Jones N, Jewett M, Cuthbert W, Rasamoelisolo M, Entwistle J, MacDonald G, Glover N. A Phase I/II Study of Vicinium™ Given by Intravesical Administration in Patients with Superficial Transitional Cell Carcinoma of the Bladder: Phase I Final Results (abstract). American Urological Association (AUA) 2010 Annual Scientific Meeting, May 29-June 3, 2010.

Jewett M, Jones N, Cuthbert W, Rasamoelisolo M, Entwistle J, MacDonald G, Glover N. A Phase I/II Study of Vicinium™ Given by lntravesical Administration in Patients with Superiicial Transitional of the Bladder: Phase I Final Results (poster). American Urological Association (AUA) 2010 Annual Scientific Meeting, May 29-June 3, 2010.

Brown JG, Entwistle J, Glover N, Macdonald GC. “Preclinical Safety Evaluation of Immunotoxins.”Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials. Edited by Joy A. Cavagnaro. Published Online: 15 Mar 2010. DOI: 10.1002/9780470571224.pse188.

Kowalski M, McCann E, Jones N, Niforos D, Chapman W, MacDonald G. Level Of Expression of EpCAM and Response to Vicinium™ in Non Muscle-Invasive Transitional Cell Carcinoma of the Bladder (abstract). European Urology Supplements, Volume 9, Issue 2, April 2010, Pages 289-290. 25th Annual Congress of the European Association of Urology, April 16-20, 2010; Barcelona, Spain.

Kowalski M, McCann E, Jones N, Niforos D, Chapman W, MacDonald G. Level of Expression of EpCAM and Response to Vicinium in Non Muscle-Invasive Transitional Cell Carcinoma of the Bladder (poster). 25th Annual Congress of the European Association of Urology, April 16-20, 2010; Barcelona, Spain.

Brown J, Rasamoelisolo M, Spearman M, Bosc D, Cizeau J, Entwistle J, MacDonald GC. Preclinical Assessment of an Anti-EpCAM Immunotoxin: Locoregional Delivery Provides a Safer Alternative to Systemic Administration. Cancer Biother Radiopharm. 2009 Aug; 24(4):477-87. doi: 10.1089/cbr.2008.0579.

MacDonald GC, Rasamoelisolo M, Entwistle J, Cuthbert W, Kowalski M, Spearman MA, Glover N. A Phase I Clinical Study of Intratumorally Administered VB4-845, an Anti-Epithelial Cell Adhesion Molecule Recombinant Fusion Protein, in Patients with Squamous Cell Carcinoma of the Head and Neck. Med Oncol. 2009; 26(3):257-64. doi: 10.1007/s12032-008-9111-x. Epub 2008 Oct 28.

MacDonald GC, Rasamoelisolo M, Entwistle J, Cizeau J, Bosc D, Cuthbert W, Kowalski M, Spearman M, Glover N. A Phase I Clinical Study of VB4-845: Weekly Intratumoral Administration of an Anti-EpCAM Recombinant Fusion Protein in Patients with Squamous Cell Carcinoma of the Head and Neck. Drug Des Devel Ther. 2008; 2: 105–114. Published online 2009 Feb 6.

Biggers K, Scheinfeld N. VB4-845, a Conjugated Recombinant Antibody and Immunotoxin for Head and Neck Cancer and Bladder Cancer. Curr Opin Mol Ther. 2008 Apr; 10(2):176-86.

Brown JG, Rasamoelisolo M, Cizeaua J, Bosca D, Entwistle J, Glover N, MacDonald GC. Evaluation of the Immunotoxin, Proxinium™ in Combination with Chemotherapy and Radiotherapy (abstract). AACR Annual Meeting, April 2007.

Brown JG, Rasamoelisolo M, Cizeaua J, Bosca D, Entwistle J, Glover N, MacDonald GC. Evaluation of the Immunotoxin, Proxinium™ in Combination with Chemotherapy and Radiotherapy (poster). AACR Annual Meeting, April 2007.

Fitsialos D, Quenneville J, Rasamoelisolo M, Cross M, Glover N, MacDonald G, Federico MHH, Barrios CHE, Guimarães RC, Nicolau UR. A Phase I Study of VB4-845 in Patients with Advanced, Recurrent Head and Neck Cancer on a Weekly Dosing Scheme (abstract). 2005 ASCO Annual Meeting, May 2005.

Fitsialos D, Quenneville J, Rasamoelisolo M, Cross M, Glover N, MacDonald G, Federico MHH, Barrios CHE, Guimarães RC, Nicolau UR. A Phase I Study of VB4-845 in Patients with Advanced, Recurrent Head and Neck Cancer on a Weekly Dosing (poster). 2005 ASCO Annual Meeting, May 2005.

Quenneville J, Fitsialos D, Rasamoelisolo M, Cross M, Glover N, MacDonald G. A Phase I Open-Label Study to Evaluate Safety, Tolerability and Pharmacokinetic (PK) Profile of VB4-845, an Anti-Ep-CAM Immunotoxin, in Subjects with SCCHN (poster). 2005 ASCO Annual Meeting, May 2005.

Di Paolo C, Willuda J, Kubetzko S, Lauffer I, Tschudi D, Waibel R, Plückthun A, Stahel RA, Zangemeister-Wittke U. A Recombinant Immunotoxin Derived from a Humanized Epithelial Cell Adhesion Molecule-Specific Single-Chain Antibody Fragment has Potent and Selective Antitumor Activity. Clin Cancer Res. 2003 Jul; 9(7):2837-48.

 

VB6-845d

J. Cizeau, S. Chooniedass, R. L. Dillon, A. Premsukh, G. P. Adams, G. C. MacDonald, N. Goodwin, H.L. Thompson and B. Archerd. Engineering and characterization of anti-PSMA humabody-deBouganin fusion proteins (poster). 2018 American Association for Cancer Research, April 14-18, 2018; Chicago.

R.L. Dillon, S. Chooniedass, A. Premsukh, G.C. MacDonald, J. Cizeau and G.P. Adams. VB6-845d Tumor Cell Killing Elicits Biologic Features of Immunogenic Cell Death (poster). 2018 American Association for Cancer Research, April 14-18, 2018; Chicago.

S. Chooniedass, R. L. Dillon, A. Premsukh, G. P. Aams, G. C. MacDonald, J. Cizeau. Trastuzumab and C6.5 diabody armed with deBouganin overcome drug resistance to ADCs comprised of anti-microtubule agents (poster). 2017 American Association for Cancer Research, April 1-5; Washington D.C.

S. Chooniedass, R.L. Dillon, A. Premsukh, J. Entwistle, G.P. Adams, P.J. Hudson, G.C. MacDonald, J. Cizeau. VB7-756: a HER2-specific Diabody Armed with deBouganin, a Plant Toxin with a Distinct MOA (poster). 2016 American Association for Cancer Research, April 16-20, New Orleans.

R.L. Dillon, S. Chooniedass, A. Premsukh, G.P. Adams, J. Entwistle, G.C. MacDonald and J. Cizeau. deBouganin Conjugated to Trastuzumab Overcomes Multiple Mechanisms of T-DM1 Drug Resistance (poster). 2016 American Association for Cancer Research, April 16-20, New Orleans.

Chooniedass S, Dillon RL, Premsukh A, Hudson PJ, Adams GP, MacDonald GC, Cizeau J.DeBouganin Diabody Fusion Protein Overcomes Drug Resistance to ADCs Comprised of Anti-Microtubule Agents. Molecules 2016, 21(12), 1741; doi: 10.3390/molecules21121741.

Entwistle J, Kowalski M, Brown J, Cizeau J, MacDonald JC. “The Preclinical and Clinical Evaluation of VB6-845: An Immunotoxin with a De-Immunized Payload for the Systemic Treatment of Solid Tumors.” Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical Development to Therapeutic Applications. G.L. Phillips (ed.), 2013. DOI 10.1007/978-1-4614-5456-4_19

Entwistle J, Brown JG, Chooniedass S, Cizeau J, MacDonald GC. Preclinical Evaluation of VB6-845: An Anti-EpCAM Immunotoxin with Reduced Immunogenic Potential. Cancer Biother Radiopharm. 2012 Nov;27(9):582-92. doi: 10.1089/cbr.2012.1200.271. Epub 2012 Aug 2.

Chaboureau A, Ragon I, Stibbard S, Cizeau J, Glover N, MacDonald GC. Intracellular Trafficking of VB6-845, an Immunocytotoxin Containing a De-immunized Variant of Bouganin (abstract). AACR Annual Meeting, April 2008.

Chaboureau A, Ragon I, Stibbard S, Cizeau J, Glover N, MacDonald GC. Intracellular Trafficking of VB6-845, an Immunocytotoxin Containing a De-immunized Variant of Bouganin (poster). AACR Annual Meeting, April 2008.

Brown J, Cizeau J, Rasamoelisolo M, Bosca D, Entwistle J, Glover N, MacDonald GC. Complete Regression of Ovarian Cancer Xenografts Following Treatment with the Recombinant Immunocytotoxic Protein, VB6-845 (abstract). AACR Annual Meeting, April 2006.

Brown J, Cizeau J, Rasamoelisolo M, Bosc D, Entwistle J, Glover N, MacDonald GC. Complete Regression of Ovarian Cancer Xenografts Following Treatment with the Recombinant Immunocytotoxic Protein, VB6-845 (poster). AACR Annual Meeting, April 2006.

Brown J, Cizeau J, Bosc D, Rasamoelisolo M, Entwistle J, Glover N, MacDonald GC. A Preclinical Profile of VB6-845: A Recombinant Immunotoxin for Targeting Ovarian Cancer (abstract). AACR Annual Meeting, April 2006.

Brown J, Cizeau J, Bosc D, Rasamoelisolo M, Entwistle J, Glover N, MacDonald GC. A Preclinical Profile of VB6-845: A Recombinant Immunotoxin for Targeting Ovarian Cancer (poster). AACR Annual Meeting, April 2006.

Rasamoelisolo M, Cizeau J, Bosc D, Entwistle J, Glover N, MacDonald GC. Functional and Biological Characterization of VB6-845, a Recombinant Ep-CAM-specific Fab Antibody Genetically-Linked with De-Immunized Bouganin (de-bouganin) (abstract). AACR Annual Meeting, April 2005.

Rasamoelisolo M, Cizeau J, Bosc D, Entwistle J, Glover N, MacDonald GC. Functional and Biological Characterization of VB6-845, a Recombinant Ep-CAM-specific Fab Antibody Genetically-Linked with De-Immunized Bouganin (de-bouganin) (poster). AACR Annual Meeting, April 2005.

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