Product Pipeline

Since mid 2005, PanGenetics has been assembling a pipeline of therapeutic antibodies for which it is currently preparing for the entry into clinical proof of concept studies. The figure below illustrates PanGenetics’ current pipeline. The route to clinical proof of concept clinical studies is clearly defined for PG102 and PG130. In addition to these programs, PanGenetics’ portfolio contains two exploratory programs, PG120 and PG140, for which the further development track will be dependent on additional preclinical evaluation.

PG102-Prototype

The PG102 prototype is the original anti-CD40 antibody that provided the first clinical data on safety and efficacy of the class of antibodies that antagonise CD40-mediated signaling. The CD40 pathway is one of the best studied pathways that play a role in the regulation of the immune system. After it was demonstrated that CD40 and its ligand play a central role in the regulation of the B-cells, this pathway became a prominent pharmaceutical target for drug discovery in both oncology (B-cell lymphoma) and autoimmune diseases. In the latter field, a number of projects aiming at inhibiting the interaction between CD40 and its ligand by antibodies that bind specifically to the ligand showed great promise in preclinical and clinical studies. However, this approach was seriously hampered by thromboembolitic side-effects caused by the expression of CD40 ligand on platelets.

PG102 prototype is the only antibody exerting an antagonistic effect on the CD40 receptor directly which has been clinically tested in an autoimmune indication. Based on very strong preclinical evidence, the chimeric antibody was tested in a combined Phase I/IIa clinical study in patients suffering from Crohn’s inflammatory bowel disease. During these initial studies, none of the side effects associated with the anti-ligand antibodies was observed. Furthermore, a promising trend in efficacy was observed, which warrants the further clinical exploration of this approach by PanGenetics.

PG102

After the PG102 prototype had been acquired by PanGenetics, the decision was made to generate a second generation antibody to progress proof of concept clinical trials. The prototype being a chimeric antibody, a modernised version of the molecule was produced by cutting edge deimmunisation technology with the goal of rendering the molecule completely immunological silent. The resulting molecule, PG102, is currently in full scale preclinical development and GMP manufacturing. An IND will be filed in early 2007 after which the molecule will be evaluated in a single ascending dose safety study in psoriatic arthritis patients. After completion of this initial study, the antibody will be tested in a multiple ascending dose Phase II study in the same indication. In addition, a second phase II study will be initiated in Multiple Sclerosis patients. Both Phase II studies will be powered to show clinical proof of concept and both are expected to read out in 2009.

PG130

PG130 is an undisclosed therapeutic antibody that PanGenetics licensed from Schering-Plough Corporation in November 2006. Recent scientific data supports the hypothesis that PG130 may prove to be efficacious in addressing a very important unmet medical need. PanGenetics will assume responsibility for the IND-enabling preclinical program for PG130 and will carry out initial clinical safety and efficacy evaluation to prove this hypothesis. This clinical program is expected to start in the second half of 2008. After a successful proof of concept Schering-Plough has the option to either assume exclusive responsibility for further development of the antibody or enter into a co-development arrangement with PanGenetics.

PG110

PG110 is a fully humanised antibody that binds to Nerve Growth Factor (NGF) with very high affinity. NGF is the prototypical member of the family of neurotrophin growth factors, that are involved in the growth and survival of nervous tissue. PG110 prevents the interaction of NGF with both its receptors, the high-affinity receptor TrKA and the low affinity receptor p75. This interaction plays a key role in pain transduction mechanisms in the adult peripheral nervous system. PG110 does not cross-react with other neurotrophins and exerts its inhibiting activity at lower than equimolar ratios with respect to NGF. The antibody therefore is a highly specific function-blocking molecule that is able to neutralise NGF bioactivity, both in vitro and in vivo. Based on this very promising preclinical data, the molecule is currently being prepared for an IND in late 2007, after which clinical evaluation in a relevant pain indication will commence.

PG120

PG120 is one of PanGenetics’ exploratory projects. It is an antibody that exerts an agonistic effect on the CD40 receptor. Scientific data suggests that this mechanism of action could be beneficial for the treatment of B-cell lymphoma and other B-cell mediated diseases. PanGenetics will undertake further preclinical evaluation of PG 120 to determine the optimal route forward for this antibody.

PG140

As part of the IP portfolio that PanGenetics acquired in 2005, the PG140 antibody, albeit early stage, holds a lot of promise. PG140 is an antagonist of CD86 and recent preclinical data suggests that the combination of this antibody with an antagonist of CD40, such as PG102, could induce tolerance in the transplantation setting. The induction of tolerance is generally accepted to be the holy grail of transplantation, both allogeneic and xeno. Therefore, PanGenetics will thoroughly pursue this potential during further preclinical evaluation.