SAN JUAN CAPISTRANO, CA and OSAKA, JAPAN — May 2, 2013 — Allegro Ophthalmics, LLC and Senju Pharmaceutical Co., Ltd. today announced that they have entered into a collaboration and license agreement to develop and market Allegro’s Integrin Peptide Therapy in Japan. With this collaboration, Allegro and Senju aim to improve the quality of life for patients worldwide who continue to be at risk of blindness from vascular eye diseases by establishing Integrin Peptide Therapy as the first-in-class treatment targeting integrin with an oligopeptide.

Under the terms of the agreement, Senju will acquire the rights to co-develop and market Allegro’s Integrin Peptide Therapy in Japan as an intravitreal injection for vascular eye diseases such as wet age-related macular degeneration (AMD) and diabetic macular edema (DME). In exchange for these rights, Senju has agreed to pay Allegro an eight-digit upfront license fee, additional development and sales milestone fees, and a percentage royalty on net sales.

“Allegro is very pleased to have formed this strategic partnership with one of the leading ophthalmic pharmaceutical companies in Japan,” said Marc Kirshbaum, Chief Operating Officer, Allegro Ophthalmics. “In addition to validating the potential of Integrin Peptide Therapy as an additional treatment option for millions of patients at risk of blindness, this partnership provides Allegro with the capital required to significantly progress its clinical program across multiple indications and phases in the United States.”

Senju had a similarly positive outlook on the relationship. “The announcement of this partnership with Allegro further evidences Senju’s commitment to its position as a leader in ophthalmology in Japan,” said Shuhei Yoshida, Executive Vice President of Senju Pharmaceutical. “We believe that Allegro’s Integrin Peptide Therapy shows great promise as a first-in-class treatment for Wet AMD, DME, and other vascular eye indications, and we are eager to begin the process for regulatory approval in Japan.”

Summit Pharmaceuticals International, a subsidiary of Sumitomo Corporation, served as advisor to Allegro in connection with this transaction.

Allegro recently announced that it completed enrollment of a Phase Ib/IIa study in Wet AMD patients as stand-alone therapy, and commencement of a Phase Ib/IIa in combination with anti-VEGF therapy. These two human studies are in addition to a previous Phase I study in end-stage DME patients. All data from human studies, as well as studies in animals, show Integrin Peptide Therapy to be safe, well-tolerated and efficacious, including the fact that the benefit of mono-therapy is holding at least three months off-treatment in both Wet AMD and DME patients.

About Integrin Peptide Therapy

Integrin Peptide Therapy, a novel approach to treating vascular eye diseases, utilizes an oligopeptide discovered by Allegro’s founders in collaboration with Caltech. Integrin Peptide Therapy uniquely approaches multiple indications by collectively turning off the production of aberrant blood vessels, reducing the leakage of aberrant blood vessels, and inhibiting the growth of aberrant blood vessels. This novel approach has the potential to be both an effective stand-alone treatment as well as complementary to existing standard of care due to its unique mechanism of action.

To learn more about Allegro and Integrin Peptide Therapy, please visit http://www.allegroeye.com or contact Allegro’s Chief Operating Officer, Marc Kirshbaum, at mkirshbaum@allegroeye.com.

About Allegro Ophthalmics, LLC

With more than 100 years of combined experience in vision science and medicine, the leadership team at Allegro Ophthalmics, LLC is establishing Integrin Peptide Therapy as the next-generation pharmaceutical category for the treatment of wet age-related macular degeneration, diabetic retinopathy and diabetic macular edema, which together affect nearly six million Americans. Allegro Ophthalmics seeks to prevent vision loss and combat blindness, potentially offering millions an improved quality of life sustained by self-sufficient, functional vision.

About Senju Pharmaceutical Co., Ltd.

Established in 1947 and headquartered in Osaka, Japan, Senju Pharmaceutical Co., Ltd., is a company that develops, manufactures, and commercializes a variety of innovative products on a global basis, specializing in ophthalmic preparations.

MEDIA CONTACT:

Allison Potter
Pascale Communications. LLC
619.550.1867

allison@pascalecommunications.com

By Jerry Helzner, Senior Editor

For most of the past decade, anti-VEGF therapies for treating wet AMD and other retinal diseases have held center stage, hailed as great advances and far more effective than any drug or procedure previously available.

But now, a growing opinion suggests that anti-VEGF monotherapy — as important as it has proven to be — will eventually be viewed as only an intermediate step in the ongoing fight to combat retinal disease.

While anti-VEGF drugs have improved the vision and quality of life for hundreds of thousands of patients with retinal disease, these drugs do have some shortcomings. Patients and retinal specialists understandably chafe under the treatment burden that regular anti-VEGF intravitreal injections entail. In addition, some patients are not responsive to anti-VEGF therapy.

Given that opportunities exist to improve upon anti-VEGF monotherapy, numerous efforts are under way to find better drugs or less-invasive delivery systems. In the investigational pipeline for wet AMD are such concepts as pills, eye drops, sustained-release delivery systems, radiation treatments (NeoVista and Oraya) and other innovative drug-development efforts too numerous to mention here.

But in terms of what new therapies are deemed most promising, early-stage clinical trials have shown that combination drugs may have the best chance of early approval. Three combinations worth mentioning are:

► Ophthotech’s anti-platelet-derived growth factor (pdgf) drug Fovista in combination with ranibizumab has shown excellent results in a phase 1/2a clinical trial of 22 patients who were not responsive to anti-VEGF monotherapy. In a large phase 2 study encompassing 449 patients, investigator Pravin Dugel, MD, reported a combination of Fovista and ranibizumab was 62% more efficacious than ranibizumab monotherapy.

► Allergan’s DARPin (designed ankyrin repeat proteins) drug, developed along with partner Molecular Partners, showed efficacy in treating wet AMD as monotherapy in a phase 2a study. The priority now is to combine the DARPin with an anti-pdgf developed by Molecular Partners in a dual-acting combination therapy. The DARPin is also being tested in combination with ranibizumab.

► Allegro Ophthalmics’ integrin peptide (ALG-1001) is designed to shut off VEGF production at its source. The drug showed good efficacy in a small study of DME patients and will be used in a phase 1b/2a trial as monotherapy to treat wet AMD.

The excellent results demonstrated thus far by Fovista, the DARPin and ALG-1001 appear to indicate that a next-generation of combination drugs to combat retinal disease may be just over the horizon.

IN BRIEF

■ Stem cells for myopic macular degeneration. The University of California, Los Angeles (UCLA) Geffen School of Medicine has received FDA approval of its Investigator Investigational New Drug Application to initiate a phase 1/2 study using Advanced Cell Technology’s retinal pigment epithelial (RPE) cells derived from human embryonic stem cells to treat myopic macular degeneration.

The trial, led by Steven Schwartz, MD, will enroll a total of 12 patients, with cohorts of three patients in an ascending dosage format. The trial is a prospective, open-label study designed to determine the safety and tolerability of human embryonic stem cell-derived RPE cells following subretinal transplantation into patients with myopia at 12 months, the study’s primary endpoint.

■ Study of Stargardt Disease planned. The Foundation Fighting Blindness Clinical Research Institute is launching a natural history study of people affected by Stargardt Disease, which includes approximately 30,000 people in the United States. Known as ProgStar, the study has three primary goals: determine the best outcome measures to accelerate evaluation of emerging treatments; better understand disease progression for selecting future clinical trial participants; and identify potential participants for forthcoming clinical trials.

The study, taking place in nine locations worldwide, will combine both prospective and retrospective analyses. The prospective portion, for which physicians will track the progression of disease in participants, will last two years. Physicians will also retrospectively analyze disease progression by reviewing the participants’ past medical records.

Pill for Dry AMD Advances

Emixustat enters large phase 2/3 study.

BY ANDREW MATHIS, PHD, MEDICAL EDITOR

Acucela’s drug emixustat (formerly known as ACU-4427) has entered a phase 2/3 trial for the treatment of dry AMD. If successful, it will be the first drug so approved. Moreover, as a once-a-day pill with an excellent safety profile, it promises to be a convenient therapy with very high compliance.

The search for a medical treatment for dry AMD has been difficult, says trial investigator Philip J. Rosenfeld, MD, PhD, of Bascom Palmer Eye Institute in Miami, in part due to the complexity and slow progression of the disease, the absence of bone fide animal models, the lack of validated clinical trial endpoints, and the different treatment strategies that have arisen as a result of competing theories on etiology of the disease.

“There are many different scientific schools of thought when it comes to explaining the underlying cause of AMD,” Dr. Rosenfeld says. “There is irrefutable scientific evidence to support each of the different theories, yet there are gaps and inconsistencies in each of the disease-causing scenarios, which suggests that we don’t have a single disease mechanism that can be attacked. Rather, multiple mechanisms are likely involved, probably at different stages of the disease.”

While emixustat targets and modulates the visual cycle of rod photoreceptors by inhibiting the enzyme RPE65, which is responsible for the isomerization of all trans-retinyl esters to 11-cis-retinol, the end result is the downregulation of rod photoreceptor metabolic activity and the decreased accumulation of toxic byproducts within the RPE cells. These toxic fluorophores result from the retinyl esters trapped in the outer segments.

Moreover, the downregulation of photoreceptor metabolic activity should result in a reduction in energy and oxygen utilization, decreases in the turnover of rod outer segments and RPE phagocytosis of outer segments, a lower metabolic profile, and most likely, a lessening in the large amount of lipid trafficking required for the rapid turnover of these to cellular membranes.

“In essence, emixustat puts the retina and RPE in hibernation while still permitting the cone visual cycle to function so that good vision can be maintained,” Dr. Rosenfeld says. “Since most geographic atrophy arises in the region of the macula, where rod photoreceptors predominate, it stands to reason that emixustat could very well slow the progression of geographic atrophy and preserve central vision.”

In addition, Dr. Rosenfeld says if emixustat can downregulate these activities, potential exists for the use of the drug in wet AMD, as well as in preventing conversion of dry AMD into the wet form of the disease.

IN BRIEF

■ Allegro moves ahead on two studies. Allegro Ophthalmics says it has completed enrollment of its phase 1b/2a study in wet AMD in addition to beginning its second diabetic macular edema (DME) trial. This second DME study is masked and will determine the additional clinical benefit of therapy with ALG-1001 (Integrin Peptide Therapy) in combination with bevacizumab (Avastin) versus bevacizumab alone. The wet AMD trial is a dose-ranging, monotherapy study with a primary endpoint of safety and a secondary endpoint of improvement in both BCVA and OCT central macular thickness.

According to the DME Study design, 30 subjects will be 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, the subjects will be observed for 30 days off-treatment for a total 120 days of observation.

ALG-1001 is a small molecule and a crucial agent in Integrin Peptide Therapy, a newly developed approach to treating vascular eye diseases. Allegro says by utilizing a small molecule discovered by the company’s founders in collaboration with The California Institute of Technology, Integrin Peptide Therapy uniquely approaches these indications by collectively turning off the production of aberrant blood vessels, reduces the leakage of aberrant blood vessels and inhibits the growth of aberrant blood vessels. Allegro says this novel approach has the potential to be both an effective stand-alone treatment as well as a complement to existing standard of care due to its unique mechanism of action.

Danger of Driving With Blind Spots

AMD patients fail simulator test.

A study using a simulator and testing the driving ability of AMD patients with central vision loss against individuals with normal vision showed that patients with blind spots can be a major danger on the roadways. The research, led by Matthew Bronstad, PhD, of the Harvard Medical School, appeared in the January 17 online edition of JAMA Ophthalmology.

The researchers set out to determine how central field loss (CFL) affects reaction time to pedestrians. They also wanted to test the hypothesis that scotomas lateral to the preferred retinal locus will delay detection of hazards approaching from that side. In the United States, individual states do not test drivers for central blind spots, although this type of testing is done in the United Kingdom and other countries in Europe.

Eleven participants with binocular CFL (scotoma diameter, 7°-25°; visual acuity, 0.3-1.0 logMAR) using lateral preferred retinal fixation loci and 11 matched controls with normal vision drove in a simulator for approximately 90 minutes per session for two sessions a week apart. Participants responded to frequent virtual pedestrians who appeared on either the left or right sides and approached the participant’s lane on a collision trajectory.

The CFL participants had more detection failures for pedestrians who appeared in areas of visual field loss than did the controls in corresponding areas (6.4% vs 0.2%). The CFL participants reacted more slowly to pedestrians in blind than non-scotomatous areas (4.28 vs 2.43 seconds) and had far more late and missed responses than controls (29% vs 3%). Scotoma size and contrast sensitivity predicted outcomes in blind and seeing areas, respectively. Visual acuity was not correlated with response measures.

The researchers concluded that in addition to causing visual acuity and contrast sensitivity loss, the central scotomas delayed hazard detection even though small eye movements could have potentially compensated for the loss. Responses in non-scotomatous areas were also delayed, although to a lesser extent, possibly because of the eccentricity of fixation.

REFERENCE:

Bronstad PM, Bowers AR, Albu A, Goldstein R, Peli E. Driving with central field loss I: effect of central scotomas on responses to hazards. JAMA Ophthalmol. 2013;131:303-309.

Link to article on Retinal Physician website: http://www.retinalphysician.com/articleviewer.aspx?articleID=108224

In addition to its effects in DME, this molecule can induce posterior vitreous detachment.

A new small molecule, a synthetic oligopeptide that holds promise as a novel modality for treating neovascular diseases of the eye, has also demonstrated the ability to induce posterior vitreous detachment (PVD) in early clinical investigation.

This peptide, dubbed ALG-1001 (Allegro Ophthalmics, LLC), operates via a number of mechanisms that may make it a valuable addition to our therapeutic arsenal, if the positive results seen to date in early clinical trials are sustained in future investigations. ALG-1001 works via a pathway distinctly different from VEGF inhibition, targeting different aspects of the angiogenic cascade. In addition to the potential for use as a standalone therapy for retinal vascular diseases, therefore, it offers the possibility of synergistic or at least additive efficacy when used in combination with anti-VEGF treatment.

Read More on Retina Today 

Studies to Further Demonstrate The Safety and Efficacy of ALG-1001

SAN JUAN CAPISTRANO, CA- February 28, 2013 — Allegro Ophthalmics, LLC, today announced that it has completed enrollment of its Phase Ib/IIa study in wet age-related macular degeneration (wet AMD) in addition to commencing its second diabetic macular edema (DME). This second DME study is masked and will observe the additional clinical benefit of therapy with ALG-1001 (Integrin Peptide Therapy) in combination with bevacizumab (Avastin) versus bevacizumab alone.

The Wet AMD Study 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). Dr. Peter Kaiser will present the results of this study in a paper presentation at The Association for Research in Vision and Ophthalmology Annual Meeting on May 6, 2013 at 3:15 pm in Room 618-620.

The objective of the recently commenced DME Study is to evaluate the safety and efficacy of ophthalmic intravitreal injection of ALG-1001 in combination with bevacizumab versus bevacizumab alone in patients with baseline DME that has not been resolved by repeated intravitreal anti-VEGF treatments. Based on results from earlier studies of end-stage DME subjects receiving ALG-1001 monotherapy, the study expects to find both reduced CMT and improved BCVA in subjects with unresolved baseline DME as a result of the combination therapy.

According to the DME 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, the subjects will be observed for 30 days off-treatment for a total 120 days of observation.

ALG-1001 is a small molecule and a crucial agent in Integrin Peptide Therapy, a newly developed approach to treating vascular eye diseases. By utilizing a small molecule discovered by Allegro Ophthalmics’ founders in collaboration with The California Institute of Technology, Integrin Peptide Therapy uniquely approaches these indications by collectively turning off the production of aberrant blood vessels, reduces the leakage of aberrant blood vessels, and inhibits the growth of aberrant blood vessels. This novel approach has the potential to be both an effective stand-alone treatment as well as complementary to existing standard of care due to its unique mechanism of action.

“The results of both of these studies could advance the potential of a paradigm shift in how we treat wet AMD and DME patients at risk for blindness,” said Vicken Karageozian, M.D., Co-Founder and Chief Technology Officer, Allegro Ophthalmics. “While the current standard of care continues to benefit many patients, we need additional treatment options, as well as more effective treatments that will allow patients living with vascular eye diseases to experience and maintain excellent vision.”

Funding for both studies has been made possible by a grant to The Wilmer Eye Institute at Johns Hopkins University from the Leona M. and Harry B. Helmsley Charitable Trust and a Series A investment round led by private individuals, including industry pioneers.

To learn more about Allegro Ophthalmics and Integrin Peptide Therapy, please visit http://www.allegroeye.com or contact Marc Kirshbaum, Chief Operating Officer, Allegro Ophthalmics, at mkirshbaum@allegroeye.com.

About Allegro Ophthalmics, LLC

With more than 100 years of combined experience in vision science and medicine, the leadership team at Allegro Ophthalmics, LLC is establishing Integrin Peptide Therapy as the next-generation pharmaceutical category for the treatment of wet age-related macular degeneration, diabetic retinopathy and diabetic macular edema, which together affect nearly six million Americans. Allegro Ophthalmics seeks to prevent vision loss and combat blindness, potentially offering millions an improved quality of life sustained by self-sufficient, functional vision.

Researchers have reported encouraging results from the first human study of a new type of antiangiogenic drug being developed by Allegro Ophthalmics, said lead investigator David S. Boyer, MD, of Los Angeles.

The drug, which currently goes by the designation ALG-1001, is a synthetic anti-integrin oligopeptide. In the initial human study, the objective was to evaluate the safety of intravitreal ALG-1001 in humans with end-stage DME, with a primary endpoint of observing dose-limiting toxicity.

Integrin peptide therapy is a new approach to treating neovascular eye diseases. A small molecule, ALG-1001, interferes with several pathways of the angiogenic cascade by binding to multiple integrin-receptor sites known to be implicated in both choroidal and preretinal neovascularization.  Read More Here.

FORT LAUDERDALE, Fla. — An integrin peptide therapy has begun a phase 1b/2a study for the treatment of wet age-related macular degeneration, according to a speaker here.

“Having completed the first human study in end-stage [diabetic macular edema] patients, a phase 1b/2a study with ALG-1001 (Allegro Ophthalmics) is currently in progress,” David S. Boyer, MD, said at the Association for Research in Vision and Ophthalmology meeting. “This 6-month, dose-ranging phase 1b/2a study is in wet AMD (as opposed to DME) with the primary goals of safety, efficacy, optimal dosage and duration of effect.”

The first subject was enrolled in April, and the study now includes 30 subjects with moderate wet AMD, Dr. Boyer said.

Integrin peptide therapy is an emerging new class of treatment for vascular eye diseases, Dr. Boyer said, and it may provide additional options and patient benefits compared with current anti-VEGF treatment.

• Disclosure: Dr. Boyer receives financial support, is a consultant with and receives other reimbursements from Alcon, Allergan, Genentech and Regeneron. He is a consultant with Allegro, Neurotech and Novartis/QLT. He receives financial support from iCo. He receivers other reimbursements from Novartis and Pfizer.

Ocular Surgery News Latin America Edition, July/August 2012
Una terapia peptídica con integrina ha comenzado un estudio de fase 1b/2a para el
tratamiento de la degeneración macular exudativa relacionada a la edad, según un
orador.
“Al haber completado el primer estudio humano en los pacientes de etapa final [edema
macular diabético], se encuentra actualmente en progreso un estudio de fase 1b/2a con
ALG-1001 (Allegro Ophthalmics),” dijo el Dr. David S. Boyer. “Este estudio de fase
1b/2a, de 6 meses y de rango de dosis es en DMRE exudativa (en contraposición al
EMD) con los principales objetivos de seguridad, eficacia, dosis óptima y duración del
efecto.”
El primer sujeto se inscribió en abril y ahora el estudio incluye 30 sujetos con DMRE
exudativa moderada, dijo el Dr. Boyer.
La terapia peptídica con integrina es una nueva clase emergente de tratamiento para las
enfermedades vasculares del ojo, dijo el Dr. Boyer, y puede proporcionar opciones
adicionales y beneficios para el paciente en comparación con el tratamiento actual anti-
VEGF.