Preclinical Studies Demonstrate Galimedix Therapeutics’ Investigational Compound GAL-101 Shows Neuroprotective Effect from Toxic Amyloid-Beta in Dry AMD and Glaucoma Models

KENSINGTON, Md. and SHORASHIM, Israel, May 08, 2019 (GLOBE NEWSWIRE) — Galimedix Therapeutics, which is developing new solutions for ophthalmic and neurodegenerative diseases, today presented data demonstrating its novel, first–in–class, investigational compound GAL–101 provides neuroprotection from misfolded amyloid beta molecules aggregating into toxic forms in vitro, neutralizing their ability to be toxic to neural tissues. Further, investigators discovered that peak levels from a single delivery of the compound may provide sustained detoxification. The poster was presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Vancouver, British Columbia, Canada from April 28 to May 2, 2019.

"The unique mechanism of action of GAL–101 has been shown to reduce the levels of amyloid beta present in the retina, thereby both preventing neurodegeneration and increasing the chances of preventing vision loss. However, this poster further demonstrates that a single peak administration of the compound by eye drops may also provide a sustained detoxifying effect in dry AMD and glaucoma patients," commented Dr. Hermann Russ, lead author of the paper and Chief Scientific Officer of Galimedix. "These preclinical data, combined with a positive result in the Phase 1 study have made it possible for us to move rapidly toward a Phase 2 program for which we will provide updates when available."

In the poster, investigators reported that eye drops of GAL–101 in repeated monkey models resulted in concentrations in the retina rapidly reaching levels far in excess of the threshold for initiating the peak–related pharmacological effect, and remained in those levels for at least four hours. Furthermore, in age–related macular degeneration (AMD) mouse models with substantial amyloid beta deposits in the retina accumulated during many months, GAL–101 eye drops when given for 1–3 months resulted in substantially less amyloid beta deposits, and simultaneously reduced the levels of C–complement response, which is considered a central factor leading to the progression of dry AMD.

About GAL–101
GAL–101 is a proprietary compound designed to prevent the formation of all forms of toxic amyloid beta oligomers, by binding with high affinity to the misfolded amyloid beta monomers before they can form toxic soluble oligomers. These then rapidly conglomerate into amorphous, non–beta–sheet formations, which we call "clusters," which are innocuous. Interestingly, once GAL–101 concentration reaches effective levels it "triggers" formation of the "clusters", which then have shown the capacity to collect additional misfolded amyloid beta monomers even in the absence of additional GAL–101 molecules, through a self–propagation mechanism. This novel "trigger effect," protected by Galimedix' patent portfolio, results in a sustained effect lasting far longer than the time a single administration of the drug remains at therapeutic levels in the retina, potentially allowing for a convenient interval application regimen for patients. Thus, GAL–101 drops may potentially provide sustained prevention of formation of toxic amyloid beta oligomers in the retina, leading to a reduction of complement response and their consequent damage. Thus GAL–101 could contribute to slowing or stopping progression, and possible restoration of neural function depressed by the chronic toxic attack.

About Galimedix
Based in the United States and Israel, Galimedix is a Phase 2 ready ophthalmic pharmaceutical company with a world class drug development team advancing a novel, patented small molecule drug with a novel MOA addressing glaucoma and dry AMD utilizing an eye drops delivery platform, which may offer significant safety and compliance advantages over commonly used direct ocular injections. Eye drops are used to deliver steroids and other small molecules, like GAL–101, to the retina, and studies with Galimedix's eye drops in monkeys have demonstrated therapeutic levels quickly reaching the retina of the closest model to humans. Compelling efficacy data from GAL–101 eye drops in relevant animal models have demonstrated more than 90 percent neuroprotection, and the compound is supported by several leading experts in glaucoma and in dry AMD who also support the design of the company's proposed Phase 2 studies.

Galimedix has exclusive worldwide license from Tel Aviv University, following return of license by a German pharma (Merz) due to management change and strategic pivot away from neuroscience. The license also includes a next generation, potentially superior molecule intended for oral delivery, with potential to treat retinal and other CNS diseases.

Jules Abraham
Core IR

US Withdrawal From Iran Nuclear Deal: One Year On

By Dan Smith
STOCKHOLM, May 8 2019 – On 8 May last year, US President Donald J. Trump announced that the United States would pull out of the Joint Comprehensive Plan of Action (JCPOA), which sets limits on Iran’s nuclear programme to ensure that it cannot produce nuclear weapons.

Despite the US withdrawal, the JCPOA remains in force; it is a multilateral agreement to which seven of the original eight parties still adhere.

When they arrived at the agreement in July 2015, the parties to it were Iran, the USA, China, Russia, France, Germany, the United Kingdom and the European Union. A few days after the JCPOA was agreed, it was endorsed by the United Nations Security Council.

The JCPOA limits Iran’s uranium enrichment programme until 2030 and contains monitoring and transparency measures that will remain in place long after that date. Along with other international experts, SIPRI’s assessment from the outset has been that the agreement is technically sound with robust verification procedures.

The International Atomic Energy Agency (IAEA) is responsible for monitoring Iran’s JCPOA implementation. It has consistently found that Iran is fully living up to its undertakings. In short, well-crafted and properly implemented, the JCPOA closes off Iran’s pathway to nuclear weapons, should it decide to go in that direction.

The 15-member UN Security Council unanimously endorsed the Iran nuclear deal in July 2015.

However, Saudi Arabia, Israel and most US Republican politicians opposed the agreement. Donald Trump made abandoning the deal a keynote of his 2016 election campaign.

Like most other critics, he has described as major flaws the JCPOA’s temporary nature and its lack of controls on Iran’s ballistic missile programme. He is also highly critical of Iran’s actions in Syria and elsewhere in the region, which he characterizes as its ‘malign behaviour’.

This makes it clear that, rather than an evidence-based technical objection to the agreement or its implementation, the US decision to withdraw from the JCPOA was a political measure aimed against Iran.

The time-limited nature of the JCPOA is by no means unique—the major US-Russian strategic arms control agreement, for example, expires in 2021. It is normal in such cases to find an appropriate opportunity to discuss extending the agreement.

Regardless of its views about Iran’s regional policies and actions—or, indeed, about the policies and actions of its regional rivals such as Israel and Saudi Arabia—the US withdrawal from the JCPOA is ill-conceived and regrettable for many reasons.

It undermines the value of multilateral diplomacy and raises questions about the sanctity and sustainability of interstate agreements.

Furthermore, it challenges the authority of the UN Security Council, which has unanimously passed a resolution endorsing the JCPOA and calling on all UN member states as well as regional and international organizations to take action to support the agreement’s implementation.

US withdrawal from the JCPOA risks seriously weakening trust and confidence in international institutions and arrangements that are essential parts of the global security architecture.

In particular, the US action undermines the global effort for nuclear non-proliferation by sabotaging an important and effective anti-proliferation agreement. It is to be hoped that the remaining parties to the JCPOA will find ways to support its continued implementation.

From Sanctioning Iran to War?

By Haider A. Khan
DENVER, May 8 2019 - With the recent military moves announced uncharacteristically by the White House first, the world is witnessing with grim fascination what could turn out to be the early moves towards a war against [...] Read more »