Partnering

Compound from a novel series of small molecules which display promising in vitro and in vivo profiles in protecting against the toxic effect of soluble β-amyloid assemblies. Potential drug candidate for the treatment of Alzheimer's disease and other related toxic protein accumulation / aggregation diseases.

Angiotensin Therapeutic Vaccine (ATV) is a therapeutic vaccine in development for the long-term control of high blood pressure. It aims to address a significant unmet medical and pharmacoeconomic need that persists despite the availability of effective therapies, the lack of sufficient patient compliance which negates the known benefits.

ATV consists of the angiotensin I peptide conjugated to carrier protein KLH (Keyhole Limpet Hemocyanin), in combination with our proprietary vaccine adjuvant CoVaccine HT^™.  ATV is thought to target the Renin Angiotensin System (RAS); a well-established pathway involved in the control of blood pressure, and has been studied in both non-clinical models of hypertension and in clinical trials in healthy human volunteers and hypertensive patients.

In the most recent Phase IIa trial investigating the safety and efficacy of ATV in subjects with mild to moderate hypertension, ATV treatment showed encouraging preliminary data in relation to differences observed between ATV and control groups in respect of antibody response and other measures.¹

Clinical trial scale cGMP batches have been manufactured for both components of ATV (angiotensin I peptide conjugate and the CoVaccine HT^™ vaccine adjuvant). CoVaccine HT^™ adjuvant has a fully synthetic manufacturing process.

ATV has broad patent protection, including issued and pending patents, potential biologic data exclusivity upon regulatory approval, together with manufacturing know-how and trade secrets.

ATV is an exciting and innovative partnering opportunity for the potential long-term control of high blood pressure. We are seeking a world-class cardiovascular partner with strength in vaccines/biologics to advance its development and commercialisation.

Reference:

1. BTG press releases, H1 2009.

CoVaccine HT^™ is an oil-in-water vaccine adjuvant consisting of synthetic sucrose fatty acid sulphate esters (SFASE) immobilised on the oil droplets of a submicron emulsion of squalane in water.

In keeping with other lipopolysaccharide (LPS) mimetic containing adjuvants, CoVaccine HT^™ has been shown to elicit its effect through toll-like receptor 4 (TLR4) signalling.³ It has also been evaluated with many vaccine antigens in nonclinical and clinical assessments.^{1,2,3,4,5,6,7,8} It has shown superior antibody responses relative to a number of other adjuvants whilst still generating antigen specific cellular immune responses.^2,4,5,6

CoVaccine HT^™ has been administered to humans as part of a healthy volunteer dose finding study for the vaccine adjuvant alone, and also in patient settings for the development of two therapeutic vaccines (Angiotensin Therapeutic Vaccine (ATV) and PEP223 in Prostate Cancer).

The vaccine adjuvant has broad patent protection, and a robust fully synthetic manufacturing process to cGMP, that is amenable to further scale up and is transferable.

CoVaccine HT^™ development is continuing through in-house programmes, external collaborations, and independent research via key institutions.

We are actively engaging with companies who are looking to enhance their vaccine portfolios by partnering a novel vaccine adjuvant that provides both a superior qualitative and quantitative immune response.

 References:

1. Blom A, Hilgers L (2004). Sucrose fatty acid sulphate esters as novel vaccine adjuvants: effect of the chemical composition. Vaccine 23 (2004) 743–754
2. Rosul A, Hargrave I, Glover J, Auton T, Waterman S, Dowhnam M (IMV 2005) Immunopotentiators in Modern Vaccines
3. Bodewes R, Geelhoed-Mieras M, Heldens J, Glover J, Lambrecht B, Fouchier R, Osterhaus A, Rimmelzwaan G (2009). The novel adjuvant CoVaccine HT^™ increases the immunogenicity of cell-culture derived influenza A/H5N1 vaccine and induces the maturation of murine and human dendritic cells in vitro. Vaccine 27 (2009) 6833-6839
4. Bodewes R, Kreijtz J, van Amerongen G, Geelhoed-Mieras M, Verburgh R, Heldens J, Bedwell J, van den Brand J, Kuiken T, van Baalen C, Fouchier R, Osterhaus A, Rimmelzwaan G (2010). A single immunization with CoVaccine HT^™-adjuvanted H5N1 influenza vaccine induces protective cellular and humoral immune responses in ferrets. J. Virol. (2010) 7943–7952
5. Kusi KA, Faber BW, Riasat V, Thomas AW, Kocken CHM, et al. (2010) Generation of Humoral Immune Responses to Multi-Allele PfAMA1 Vaccines; Effect of Adjuvant and Number of Component Alleles on the Breadth of Response. PLoS ONE (2010)
6. Draper S, Biswas S, Spencer A, Remarque E, Capone S, Naddeo M, Dicks M, Faber B, de Cassan S, Folgori A,  Nicosia A, Gilbert S, Hill A (2010). Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines. J. Immunology (2010)
7. Heldens J.G.M, Glansbeek H.L, Hilgers L.A.T, Haenen B, Stittelaar K.J, Osterhaus A.D.M.E, van den Bosch J.F. Feasibility of single-shot H5Nl influenza vaccine in ferrets, macaques and rabbits (2010). Vaccine 28 (2010) 8125-8131
8. Mahdi Abdel Hamid M, Remarque EJ, van Duivenvoorde LM, van der Werff N, Walraven V, et al. (2011) Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HTTM Protects against Blood-Stage Challenge in Rhesus Macaques. PLoS ONE 6(5): e20547. doi:10.1371/journal.pone.0020547

Novel small molecule which suppresses β-amyloid1-42-induced macrophage production of nitric oxide, TNF-α, IL-1β and IL-6 in preclinical studies.  Displays good oral bioavailability and efficacy in an in vivo model of learning and memory.  Has potential for the treatment of chronic neuroinflammatory processes related to brain Aβ deposition in Alzheimer's disease and other neuroinflammatory diseases.

We’re developing Varisolve^® (polidocanol endovenous microfoam (PEM)) as a first line treatment for incompetent great saphenous veins (GSV) and associated varicosities, above and below the knee.

In the US alone over 40 million patients suffer from varicose veins.¹ Most sufferers opt not to have their veins treated, as current treatments require either the surgical removal of the vein or insertion of a catheter. As potentially the first approved drug, PEM could transform this underserved market by making varicose vein treatment more acceptable.

PEM has a controlled density, consistent bubble sizes, and proprietary gas mix that makes it a simple and comprehensive treatment for symptomatic and aesthetic varicose veins. A European Phase III clinical trial showed that 90% of patients treated with PEM had no reflux in the GSV at 3 months and fewer than 10% of patients had recurrence at 1 year. Patients can generally return to work or their usual activities the same day they are treated, and cosmetic results after PEM treatment are apparent at 6 weeks.¹

Results of three Phase III US trials of Varisolve^® were reported in the first half of 2012.

The two pivotal US trials, VANISH-1 and VANISH-2 had relief of symptoms as the primary endpoint and improvement in appearance as the secondary endpoint. Both trials met all primary, secondary and tertiary endpoints with a high degree of statistical significance. This is the first time patient benefit has been shown using patient-reported outcome measures in pivotal Phase III trials in patients with varicose veins.

A third, smaller study (VV017) separately evaluated patients treated first with heat ablation of the great saphenous vein (GSV) followed by treatment with PEM or placebo for the remaining visible varicosities. Appearance was measured by co-primary endpoints, a blinded independent panel review of photographs and a patient-reported measure of appearance. Relative to baseline, all PEM treatment groups demonstrated a greater improvement in appearance than placebo by both measures. One co-primary endpoint was met with statistical significance but not the other, hence the primary objective of the study was not achieved.

Based on the successful outcome of the two pivotal US Phase III trials, BTG intends to submit a New Drug Application in the US, seeking approval of PEM as a comprehensive treatment for symptoms and appearance of varicose veins by the end of 2012. We plan to market and sell PEM directly in the US reimbursed sector following approval.

References:

1. Wright et al, Phlebology 2006. Vol .21 No. 4

High-dose methotrexate is used to treat or prevent the recurrence of certain types of cancer. Patients are considered at risk of methotrexate toxicity if they have impaired renal function, which can lead to a delay in elimination from the body. Patients are also considered at risk of methotrexate toxicity if they have evidence of delayed elimination based on high methotrexate levels in the blood.

We recieved US regulatory approval for Voraxaze^® (glucarpidase) in early 2012 for the treatment of toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function. In April 2012 we launched Voraxaze^® in the US and sell this direct to specialist physicians through our specialty pharmaceuticals sales force.

We would be interested in discussing partnering opportunities for territories outside of the US, Europe and Japan with commercialisation partners who would be able to complete the final development and regulatory steps to secure approval in those countries.