Current treatment options for vascular eye diseases such as wet macular degeneration and diabetic macular edema simply sequester pre-existing VEGF supply. Operating from a different mechanism of action, Allegro’s Integrin Peptide Therapy with its extremely small molecule turns off VEGF production at a much earlier stage of the angiogenic cascade. This unique mechanism of action in conjunction with the small size of the molecule means that introducing Allegro’s drug as the first new class of therapeutics will potentially provide an additional benefit to patients over current standard of care for vascular eye diseases, while also having the potential to be dosed topically in the future.
Allegro has proven the safety and efficacy of its molecule in vitro and in vivo in animal models as well as in humans.
Studies to date show that Allegro’s compound inhibits cell adhesion in vitro and arrests aberrant blood vessel growth in vivo, both systemically as well as in the eye. Allegro’s in vitro testing has shown that its compound inhibits cell adhesion meditated by α5β1, αvβ3 and αvβ5 integrins. Integrins α5β1, αvβ3, and αvβ5 are implicated in the angiogenic process, and are known to be expressed in neovascular ocular tissue from patients with wet macular degeneration and diabetic retinopathy.
Over the past year, ophthalmic preclinical safety studies of Allegro’s compound in rabbits and mice with both a single injection as well as repeated multiple injections have shown excellent initial safety and efficacy profiles. Allegro’s compound produces rapid, complete liquefaction of the rabbit vitreous and induces PVD within one to two days with no apparent toxicity or immunologic side effects.
Additionally, Allegro’s compound demonstrated a statistically significant regression in neovascularization in both a well-published CNV mouse model and a well-published ROP model conducted by Dr. Peter Campochiaro at Johns Hopkins University.
Dr. Campochiaro’s third study showed comparable rates of efficacy in regressing CNV in Wet AMD between ALG-1001 and the gold standard of care (i.e., Lucentis) stand-alone using a mouse model that expresses human VEGF. Of even greater interest was the fact that the combination of ALG-1001 and Lucentis performed 35% better than either drug stand-alone – with statistical significance.
Lastly, in the same hVEGF model, Dr. Campochiaro proved with statistical significance that ALG-1001 reduced vascular leakage.
Allegro completed its Phase I Human Safety Study in 2011 with 15 end-stage DME patients receiving three monthly intravitreal injections of ALG-1001. These patients were then followed for an additional three months off-treatment. No study subjects experienced serious or significant adverse events. While this study was firstly a safety study, efficacy data shows that 8 of 15 patients improved three to five lines on the eye chart, 4 of whom have improved from legally blind to functional vision in the 20/40 to 20/60 range. Also, 8 of 15 patients have experienced a 30% to 80% reduction in the thickness of their macula – an important factor impacting vision. These results have been achieved despite the fact that these first patients are end stage, several failed to respond to Avastin and some have proliferative diabetic retinopathy.
Allegro’s scientific advisors first presented the results from the Company’s Phase I Study in October 2011 at the American Academy of Ophthalmology Conference, and an update with further data was provided at The Association for Research in Vision and Ophthalmology Conference in May 2012. The results and continued progress have also been shared at numerous additional domestic and international medical and scientific conferences.
Allegro has completed enrollment in its Phase Ib/IIa Wet AMD Study. This is a dose-ranging, monotherapy study with a primary endpoint of safety and a secondary endpoint of improvement in both best corrected visual acuity (BCVA) and OCT central macular thickness (CMT). Subjects received three monthly injections and are being followed off-treatment for an additional four months.
Allegro has also commenced its second diabetic macular edema study. This second DME study is masked and will observe the additional clinical benefit of therapy with ALG-1001 in combination with bevacizumab (Avastin) versus bevacizumab alone. According to the study design, 30 subjects are being divided into three groups. Two groups will receive four monthly intravitreal injections of Avastin plus ALG-1001 (at two different doses of ALG-1001) . The third group will receive four monthly intravitreal injections of Avastin and a sham injection. After the four monthly injections, all subjects will be observed for 30 days off-treatment for a total 120 days of observation.