StemCell Therapy

ANN ARBOR, MI -Irreversible blindness affects at least 11 million Americans and 170 million across the world, according Michigan Medicine officials.

One of the leading factors of this condition is a disease called age-related macular degeneration, and an $11.5-million gift to the health system seeks to make the irreversible reversible.

The philanthropy from James Grosfeld, former chairman and CEO of PulteGroup Inc., goes toward research at the University of Michigan Kellogg Eye Center to develop effective treatments for the dry version of AMD, which affects up to 90% of those affected, officials said.

Grosfelds gift will support two endowed professorships at UM dedicated to dry AMD research, as well as increased laboratory staff. Other funded items include:

Increasing the speed and the breadth of discovery in dry AMD can make a significant difference in peoples lives, Grosfeld said in a statement.

Grosfelds enthusiasm and generosity has been greatly appreciated, said Dr. Paul Lee, director of the Kellogg Eye Center. The AMD research initiative will be led by Dr. Jason Miller, who will assume the title of the Grosfeld Professor of Ophthalmology and Visual Sciences.

We have made several discoveries that have given us a clear direction toward potential treatments, Miller said in a statement. At the same time, we have been building partnerships that will both accelerate our work and enable us to translate our efforts into clinical applications.

The AMD disease specifically attacks the part of the eye that houses the retinas light-sensitive photoreceptors. Millers research addresses how to limit the accumulation of lipids that affect these areas of the eye.

In catalyzing work across disciplines, we are enabling the creative application of a wide range of scientific techniques and approaches to the challenges of dry AMD, Dr. Marschall S. Runge, CEO of Michigan Medicine, said. Mr. Grosfelds visionary support will enable us to make important advances toward saving sight today and will create a legacy of sight-saving achievement.

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Read this article:
An end to blindness? $11M gift to Michigan Medicine researches eye treatments - MLive.com

Dynamic Culturing Process Developed by Lineage Offers Path to Clinical- and Industrial-Scale Production of Photoreceptors

CARLSBAD, Calif., April 25, 2022--(BUSINESS WIRE)--Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, today announced a new cell therapy development program: photoreceptor neural cell (PNC) transplants for the treatment of vision loss due to photoreceptor dysfunction or damage. Similar to the companys recently announced pipeline expansion into auditory neurons for the treatment of hearing loss, Lineage has filed for intellectual property protection covering the composition and methods for generating PNCs. Based on recent in vivo data generated using the companys PNCs, these cells may be capable of forming reconstructed retina with high survivability and neural connectivity to surrounding functional layers. Notably, Lineage has demonstrated feasibility which could support a large-scale method for producing both types of photoreceptors, known as rods and cones.

"It is natural that, on the heels of the announcement of our alliance with Roche and Genentech for our RPE cell therapy, a deal worth up to $670 million dollars plus double-digit royalties if certain development, approval, and sales milestones are achieved and other conditions are met, that we also would pursue treatments for vision loss through the other major cell type of the retina, the photoreceptors," stated Brian Culley, Lineages CEO. "Our fundamental technology and accumulated know-how give us the opportunity to make many different cell types, and we have demonstrated our ability to create new programs rapidly and efficiently in two distinct areas, expanding our cell therapy pipeline to five separate preclinical and clinical programs, while still maintaining what we believe is an appropriate and responsible rate of investment for a company of our size. This latest program is part of our long-term planning for clinical and commercial success and serves as another example of the capability of our technology platform. We believe our ability to, in just a matter of months, advance from a product concept to generating new intellectual property and manufacturing the desired cell types, is illustrative of the power and efficiency of our platform. We believe the combination of our capital discipline and current balance sheet will support multiple years of further progress, during which we anticipate reaching achievements with each of our clinical and preclinical programs."

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Dr. Rami Skaliter, who leads the manufacturing function for Lineage, added, "Im exceptionally proud of the teams success at overcoming obstacles related to the limited scale of photoreceptor production. Building upon our experience with other cell lineages, we have developed intellectual property, and filed for patent protections, on a manufacturing process which is compatible with large-scale production of photoreceptors in a closed system, improvements which could enable industrial manufacturing. We believe this accomplishment will provide new opportunities for clinical, and ultimately commercial, production of photoreceptors in areas of large unmet need such as Retinitis Pigmentosa, Stargardts Macular Dystrophy, and retinal detachments, either independently or through strategic alliances."

As part of a scientific collaboration with Professors Benjamin Reubinoff, M.D., Ph.D. and Eyal Banin, M.D., Ph.D., of the Hadassah-Hebrew University Medical Center, the differentiation of pluripotent cells into photoreceptors with clinically compatible characteristics was established utilizing a novel differentiation protocol which generated positive identity of key markers of both rods and cones photoreceptor populations. The data generated by the company further demonstrated that a single cell suspension of photoreceptor precursor cells has the potential to survive and mature post-transplantation in a rodent model of retinal degeneration.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include five allogeneic ("off-the-shelf") product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, which is now being developed under a worldwide collaboration with Roche and Genentech, a member of the Roche Group; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; (iii) VAC2, a dendritic cell therapy produced from Lineages VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer (iv) ANP1, an auditory neuronal progenitor cell therapy for the potential treatment of auditory neuropathy, and (v) PNC1, a photoreceptor neural cell therapy for the treatment of vision loss due to photoreceptor dysfunction or damage. For more information, please visit http://www.lineagecell.com or follow the company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as "believe," "aim," "may," "will," "estimate," "continue," "anticipate," "design," "intend," "expect," "could," "can," "plan," "potential," "predict," "seek," "should," "would," "contemplate," "project," "target," "tend to," or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to (i) the potential amount of payments to Lineage under the alliance with Hoffman-La Roche Ltd. ("Roche") and Genentech, Inc., (ii) the potential for new opportunities for clinical, and ultimately commercial, production of photoreceptors in areas of large unmet need, (iii) Lineages position to become a leader in the emerging field of regenerative medicine and anti-aging technology, and (iv) future areas of potential treatment using PNC transplant. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including, but not limited to, the risk that competing alternative therapies may adversely impact the commercial potential of OpRegen, which could materially adversely affect the payments payable to Lineage under the Roche/Genentech collaboration and license agreement, the risk that Roche/Genentech may not be successful in completing further clinical trials for OpRegen and/or obtaining regulatory approval for OpRegen in any particular jurisdiction; the risk that Lineage might not succeed in developing products and technologies that are useful in medicine and demonstrate the requisite safety and efficacy to achieve regulatory approval in accordance with its projected timing, or at all; the risk that Lineages intellectual property may be insufficient to protect its assets; risks and uncertainties inherent in Lineages business and other risks discussed in Lineages filings with the Securities and Exchange Commission (SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading "Risk Factors" in Lineages periodic reports with the SEC, including Lineages most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the SEC and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220425005336/en/

Contacts

Lineage Cell Therapeutics, Inc. IR Ioana C. Hone(ir@lineagecell.com)(442) 287-8963

Solebury Trout IR Mike Biega(Mbiega@soleburytrout.com)(617) 221-9660

Russo Partners Media Relations Nic Johnson or David SchullNic.johnson@russopartnersllc.com David.schull@russopartnersllc.com (212) 845-4242

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Lineage Announces a Fifth Cell Therapy Program: Allogeneic Photoreceptor Transplants for the Treatment of Diseases Which May Lead to Blindness - Yahoo...

The Russian invasion of Ukraine appears, on the surface, to be a land war. Newspapers lead with photographs of burned-out tanks, and on television and online we hear about the Belorussian border and truck convoys and listen to the expert commentary of generals. But this is a naval war as well.

Fighting has taken place both around the inland capitol of Kyiv, but also on the coast and over control of key port cities. While Russian explanation for new drive in the east focuses on the Russian-speaking population and territorial expansion, there is also a second and more strategic reason: the desire for a land bridge to Crimea, which would reduce the vulnerability of the Russian naval base at Sevastopol. When examining the maritime elements of the war, three points of analysis are worth consideration: first, the nature of conflict at sea and its existence out of sight of land and in a different domain which confounds our understanding; second, how the Russian navy pursued the basic elements of naval strategy reflects their continued relevance in this century; and third, the ways in which Ukraine has adapted to the conflict, and how it might make future adjustments, requires understanding of the naval past and creative thinking about the naval future.

Sea Blindness in Theory and in Practice

Over a decade ago, Butch Brakenel and James Kraska wrote that the United States suffers from a kind of sea blindness an inability to appreciate the central role the oceans and naval power have played in securing our strategic security and economic prosperity. Most use of sea blindness has tended to be metaphorical or focused on the grand economic and security connections between nations and the sea. Yet, in the Russo-Ukrainian war, the United States is experiencing sea blindness in a literal sense.

As various observers scroll through social media in search of open-source intelligence on the war, we are presented with a wealth of information that we then assess for validity and usefulness. However, very little of it is focused on the seas. Photos of burned-out T-72 tanks and trucks, video clips from targeting drones, or after-action threads that summarize changes in the fighting fill our feeds. For the most part, those of us who rely on open sources are blind to what is happening on the Ukrainian coast and in the Black Sea. The exceptions, like the final stand on Snake Island or the sinking of a Russian Alligator-class LST at the pier in Berdyansk, prove the rule. The early reports of the events surrounding the sinking of the cruiser Moskva illustrate this point also. These were based on the reposting of dueling press releases or online press reports rather than imagery, video, or on-scene information, which did not start to come until well after the fact.

A handful of media outlets and online trackers are trying to keep up with the maritime war. H.I. Sutton has been keeping the Covert Shores maritime open-source intelligence outlet going with information and writes reports for USNI News when they can confirm details. But an accurate picture of what is happening at sea is difficult. Truly actionable intelligence requires more than an occasional commercial satellite image or screenshots of maritime transponders. They involve electronic intercepts, radar, sonar, and elaborate collation and analysis efforts. All of these realities mean that while the NATO navies and Russian navy are actively producing their own maritime awareness, most of the rest of us are left in the dark about the conflict at sea.

But the fact that our Twitter feeds and Instagram scrolls are not filled with naval or maritime news does not mean that nothing is happening. It is important to remember that any war which takes place in a coastal territory (and many which take place in landlocked territory) have naval elements. The Russian invasion and Ukrainian defense of their sovereignty are no different, regardless of our sea blindness.

Retrospect: Naval Strategy in Action

As Bernard Brodie reminded us, boiled down to its simplest ideas, naval strategy can be described in a clear way. It begins with the need to establish command of the sea. It is taken further by determining what to do with the control that command of the sea offers.

Establishing command of the sea does not have to be global or even regional, but could simply be local to the area of operations. There tend to be two main ways to establish command. The first is to defeat the opponents navy or main battle fleet. By sinking the enemy, you keep them from being able to stop your use of the sea. But theres a second way to establish command, and that is to keep your opponents navy from ever putting to sea. Whether through blockade or by conducting strikes that sink them or limit their mobility while still in port, this can be equally effective.

Using the control created when you gain command of the sea is generally done in three ways. These operations are what I have previously called the 3 Bs of naval strategy: blockade, bombardment, or putting boots on the ground via amphibious landing. Naval strategy is the mixing and matching of these operations to achieve the political ends which are the purpose of the war. This effort to establish command of the sea, and then to use it, can offer us a good way to look at Russian naval operations in the first phase of the current war.

From the earliest days of the Russian invasion, the Russian navy has largely followed a classical strategy. When Russia annexed Crimea in 2014 and retook complete control of the then divided naval base at Sevastopol, where they leased facilities from Ukraine. It also took possession of nearly three quarters of the Ukrainian navy. When the Russian invasion began earlier this year, there was little more than a mosquito fleet of patrol boats to stand in their way. Russian naval forces out of Sevastopol include missile corvettes and frigates as well as some Kilo-class submarines, joined by the old Slava-class cruiser Moskva as the flagship. These were reinforced by amphibious ships from the Baltic Fleet and Northern Fleets before the invasion began. These ships largely bottled up the smaller Ukrainian patrol forces in port at the start of the war and established command of sea via blockade and strikes on Ukraines ports.

Russians quickly created a blockade of Ukraine by closing the Kerch Strait, which connects the smaller Sea of Azov to the Black Sea and established complete control of the Sea of Azov, and stationing ships off Odessa and other Ukrainian ports. The blockade remains unannounced, and therefore legally unofficial, but is in force with a de facto status. This status quo has remained unchallenged, though the wider maritime community has pointed out the negative effects on trapped neutral vessels and ships that have come under fire in the Black Sea. The resulting commercial blockade has ensured that Ukraine is cut off from the economic lifelines necessary to support its war, making the country entirely reliant on direct financial support from the West. Secondly, it eliminated the ability to resupply the Ukrainian military via the sea, which could have moved far more material far more quickly toward the fighting in the east than trucking it from the Polish border across the entire length of the country.

With total control of the Sea of Azov and the blockade holding, the Russian navy launched its first amphibious landings as a part of the offensive against Mariupol. Russian naval doctrine is designed to avoid contested amphibious landings, instead looking for a safe place to insert troops and equipment. This landing was no different, occurring approximately 30 miles southwest of the port city, away from defenders and closer to the safety of the Crimean Peninsula.

Amphibious assaults, landings made in the face of enemy defenses, are enormously difficult. The small craft used to connect amphibious ships to the shore, as well as amphibious ships like tank landing ships which can steam right up onto the beach, are enormously vulnerable to the kinds of light anti-tank weapons which have become ubiquitous in the Ukrainian defenses. Additionally, Russian amphibious forces are designed around surface landings and do not involve vertical envelopment doctrine with helicopters like many western naval services. With these limitations in mind, Russians began making pier-side reinforcement of their ground forces until the Ukrainians sank the Alligator-class amphibious ship Saratov while she was offloading at a pier in Berdyansk. The results of this attack may have made the Russians more cautious about these kinds of amphibious reinforcements, though the Pentagon spokesman has suggested resupply via sea continues.

Mariupol represents two elements that made it a key maritime target for the Russians. First, it is a significant port on the Sea of Azov and controlling it would continue to solidify that sea as a Russian lake. Second, control of Mariupol is vital to establishing a land bridge between Russian territory and the island of Crimea which is surrounded by Ukrainian territory. The Sevastopol naval base, which has been fought over for centuries as the key to the northern Black Sea, remains vulnerable so long as it is cut off from Russia itself. Annexing not only the Crimean Peninsula, but also the territory that connects it with the rest of Russia, is a classical naval mission since it secures the safety of Sevastopol.

In addition to the blockade and putting boots on the ground, from the earliest days of the invasion, Kaliber land-attack cruise missiles launched from Black Sea Fleet were a part of the bombardment. With over a thousand missiles launched into Ukraine by Russian forces it is safe to say that several hundred of those were naval strike missions, particularly around Odessa and coastal targets. Questions remain about Russian magazines of the missiles, and their ability to reload them. The loss of the Moskva, armed entirely with anti-ship and anti-air missiles, is far less significant in this regard than the Turkish closing of the Bosporus to warships, which keeps the Russians from reinforcing their fleet.

The establishment of command of the sea was followed rapidly by using the Sea of Azov and the Black Sea for operations affecting events ashore. The Sea of Azov was closed off and Ukrainian ports were blockaded, sealing off both military and commercial traffic. The Russian navy used the Sea of Azov to reinforce operations ashore and contributed to the brutal and ongoing assault on Mariupol. And the Black Sea Fleet fired hundreds of missiles in a wide-ranging bombardment that contributed to both tactical effects but also the indiscriminate destruction of civilian targets. Regardless of the legitimacy of the Russian aggression, the legality of the maritime operations, and clear movement toward war crimes, through the lens of naval strategy and in dramatic comparison to the failures of the Russian army, the Russian navy did its job effectively.

Prospect: Sea Denial and Contesting Command of the Sea

And yet, the relative success of the Russians at sea does not mean that their naval strategy is complete. Strategy is an activity that never ends. The realities of war, the contingency of human interactions, and the shifting context of conflict in an international space, all mean that the successful execution of a navys strategy can shift rudder in an instant. More often than not, that comes from a change in the enemys approach.

The trouble with command of the sea is that while it ideally would be complete and at the very least regionally enforceable, it is never totally achieved. Alfred Thayer Mahan and Julian Corbett were clear on this in their writing. They explained that while navies and naval strategists were right to aspire to a complete or total establishment of a general command of the sea, it would almost never happen in reality. In the particular case of a coastal nation fighting an expeditionary navy on its own shores, a country like Ukraine does not need to establish command of the sea for itself, it only needs to deny it to the enemy.

Despite his reputation for being focused exclusively on battleships and the battle fleet, a caricature of his actual naval writing, Mahan wrote extensively on the need for solid coastal defense as a joint army and navy mission as a part of any nations naval strategy. He broke coastal defense down into three key capabilities: shore-based gunnery, the use of mines, and small attack craft which meant torpedo boats at the dawn of the 20th century. As Jason Lancaster has written elsewhere, our modern versions of these remain available avenues of operations for Ukrainian forces as the Russian invasion shifts phases.

Today, coastal defense gunnery comes in many forms. The most obvious modern version of what used to be heavy artillery guns built into coastal fortifications are coastal defense cruise-missile systems. Rather than fixed weapons built into the stone or concrete of a coastal fort, they are often mobile and tied into a network of targeting data from radars and manned and unmanned intelligence collection systems. On April 13, 2022, Ukrainian forces reported their first successful cruise missile attacks on the Moskva. Details are unconfirmed, but we do know that the ship sank hours later while being towed to Sevastopol. While the Ukraine has a limited number of the indigenously produced Neptune missile systems, the United Kingdom has promised coastal defense cruise missiles as part of their most recent aid package. And cruise missiles are not the only weapons available for taking enemy ships under fire. The Bayraktar drones which have been used successfully against Russian armor also exist in a maritime version used by the Ukrainian navy and represent a capability that can be used against Russian warships. Additionally, munitions like the American Switchblade drones and laser-guided mortars have a more limited range but could be useful in the near littoral.

Mine warfare remains available to the Ukrainian navy as well. It is unclear to what extent it may have been used already to close off Russian operations close to shore. Russians have claimed that Ukrainians are using mines, and some have been found drifting in the Black Sea. Yet the source of those weapons is unclear, and the Russians could be using mines themselves to enhance their blockade, keeping ships from leaving port just as easily as they keep ships from entering. Mine warfare is a double-edged sword, because mining your own waters will require you to sweep them back up to make your harbors safe for commerce again, or to make them safe for resupply via sea. Ukraine may elect to use sea mines, but will likely do so in specific ways and in particular maritime geography where they are more likely to help than hurt.

Finally, coastal defense small craft remain an open question for Ukraine. The patrol vessels in its navy have already been targeted by the Russians, sinking the Solviansk in the first week of March. However, when it comes to small craft, the conversion of civilian vessels to military purposes is far easier than with medium to larger vessels. While it would likely be too difficult to mount British-supplied Harpoon missiles on small craft, the mortar tubes used to launch Switchblade drones and laser-guided mortars would be rather easy to bolt onto the aft deck of a civilian fishing or pleasure craft repurposed as naval raiders. Additionally, a recent list of new security assistance assets from the U.S. government includes Unmanned Coastal Defense Vessels. What these vessels look like, or their capabilities, are not clear since the U.S. Navy does not actively deploy anything that fits that description. It appears that the sinking of the Moskva has caused Russian warships to push themselves further offshore in order to avoid missile attacks. This transitions what had been a relatively close blockade to a far blockade and potentially opens up the seas for Ukrainian small craft to begin operating.

Naval Warfare in the Black Sea

In the first phase of the Russian war on Ukraine, the Russian navy largely succeeded in the basics of establishing a coherent naval strategy. It quickly established command of the sea by keeping Ukrainian ships from sailing. Once control of the waters of the southern coast of Ukraine and the Sea of Azov was established, the Russians began using it for their military purposes by blockading the coast, launching naval bombardments of targets both on the coast and well inland, and by landing boots on the ground with amphibious reinforcements of existing operations. Attempts to resupply Russian forces via the sea have been a mixed bag, with some success and some spectacular failures like the sinking of a Russian amphibious ship pier-side at Berdyansk. But the war on shore has entered a second phase. As Ukraine begins amassing more sophisticated and capable weapons, Russian forces face limitations due to the limited Turkish closure of the Bosporus under the terms of the Montreux Convention. The war at sea can shift as well.

The adoption of the classical methods of coastal defense, through the use of coastal gunnery and strike capabilities, careful employment of mine warfare, and adopting a creative approach to small craft, might allow Ukrainian forces to challenge Russian command of the sea. While they do not need to gain command for themselves, the ability to deny Russia easy and open use of the Black Sea and Sea of Azov could provide Kyiv with major benefits. The stunning sinking of the Moskva may be the turning point: As the Russian warships pull back from the coast to better protect themselves, they open more littoral maneuver space for Ukrainian forces. The adoption of greater coastal defense measures, combined with a limited guerre de razzia strategy that might even put the facilities as Sevastopol at risk, offers a clear naval strategy that will both limit the advantages the Russians established in the early weeks of the war while at the same time giving Ukrainian naval forces the opportunity to impose costs on Russian forces.

BJ Armstrong is a contributing editor with War on the Rocks and is the principal associate of the Forum on Integrated Naval History and Seapower Studies. His fourth book, Developing the Naval Mind, coauthored with John Freymann, was published in November. Opinions expressed in his article are offered in his personal and academic capacity, and do not reflect the positions or policies of the U.S. Naval Academy, the Department of Defense, or any other agency.

Image: Government of Ukraine

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The Russo-Ukrainian War at Sea: Retrospect and Prospect - War on the Rocks

Museum guests who are red-green colour blind can now borrow special EnChroma glasses from the Chau Chak Wing Museum and experience exhibitions for example the vast array of blue hues in theCoastlines exhibition in clear, vibrant colour for the first time.

The accessibility of art and design is always top of mind at the Chau Chak Wing Museum and we are very pleased to be the first venue in Australia to offer this technology through EnChromas Colour Accessibility Program, said DrPaul Donnelly, Deputy Director of the Museum.

This partnership is another important step forward in our inclusivity goals, helping people who are colour blind to experience the full wonder and vibrancy of the exhibitions we have on offer.

One in 12 men (8 percent) and one in 200 women (0.5 percent) arecolour vision deficient; an estimated 350 million people worldwide.More than one million Australians are colour blind, as are over 3,500 of the 83,000 students and staff at the University of Sydney.

While people with normal colour vision see overone million shades of colour, those with colour visiondeficiencyonly see an estimated 10 percent of hues and shades.As a result, colours can appear dull, indistinct, and difficult to discern.

Go here to see the original:
Glasses bring colour to the museum - University of Sydney

life-style,

As they age, animals can experience a decline in their eyesight, but occasionally, some animals lose their vision altogether. This can be particularly distressing for the animal and owner if it occurs suddenly, as animals do not have time to adapt. Sudden, total vision loss is not typical of ageing and often indicates underlying disease that needs treatment. Animals that become blind suddenly may exhibit obvious behavioural changes, and appear disoriented. There are many causes of blindness. These include diseases that affect the surface of the eye (like dry-eye), the front chamber of the eye (like cataracts), the retina (like glaucoma or retinal detachment), the optic nerves (like infection or inflammation), and those impacting the brain (like stroke or organ failure). Blindness can also occur secondary to ingestion of toxins (for example, an overdose of ivermectin) or certain cancers (particularly eye and brain tumours). Some conditions, such as diabetes, predispose animals to developing cataracts. If you suspect that your pet has gone blind, it is important to seek veterinary attention as soon as possible. It is useful for your veterinarian to know whether you have observed a change in the appearance of the eyes, any changes in the overall health of your pet, and any recent medications they have been on, as well as any changes you have noted in their behaviour. Your veterinarian will conduct a physical examination and may perform additional tests, such as blood tests and blood pressure measurement. Your pet may be referred to a veterinary ophthalmologist for further evaluation and treatment. In some cases, blindness can be reversed with treatment. For example, it is possible for detached retinas to be surgically reattached. Similarly, cataracts may be removed. My late dog Phil was almost entirely blind when cataract surgery restored his vision. Interestingly, the first thing he did with his brand new eyes was walk up to the cat's food bowl and pee in it, as if he had been waiting for the opportunity to do so for some time. Because some conditions must be treated in a narrow window of time to ensure vision can be restored, it is important to see your veterinarian early if you suspect that your pet's vision has deteriorated. Dogs and cats can adapt well to loss of vision over time, with most able to successfully navigate their way around their home. If you do live with a blind or vision-impaired dog or cat, there are a number of steps that you can take to make life easier for them: REFERENCE BIONDI, V., PUGLIESE, M., VOSLAROVA, E., LANDI, A. & PASSANTINO, A. 2022. Animal Welfare Considerations and Ethical Dilemmas Inherent in the Euthanasia of Blind Canine Patients. Animals, 12. DOI: 10.3390/ani12070913 Dr Anne Quain BVSc (Hons), MANZCVS (Animal Welfare), Dip ECAWBM (AWSEL) is a lecturer at the Sydney School of Veterinary Science and a practising veterinarian.

/images/transform/v1/crop/frm/32UQzXcwHuv6EtT6StXJwQK/f5cdfb26-d7bf-421e-a6ef-6b0d68dd2bc5.jpg/r12_0_5108_2879_w1200_h678_fmax.jpg

As they age, animals can experience a decline in their eyesight, but occasionally, some animals lose their vision altogether.

This can be particularly distressing for the animal and owner if it occurs suddenly, as animals do not have time to adapt.

Sudden, total vision loss is not typical of ageing and often indicates underlying disease that needs treatment.

Animals that become blind suddenly may exhibit obvious behavioural changes, and appear disoriented.

There are many causes of blindness.

These include diseases that affect the surface of the eye (like dry-eye), the front chamber of the eye (like cataracts), the retina (like glaucoma or retinal detachment), the optic nerves (like infection or inflammation), and those impacting the brain (like stroke or organ failure).

Blindness can also occur secondary to ingestion of toxins (for example, an overdose of ivermectin) or certain cancers (particularly eye and brain tumours).

Some conditions, such as diabetes, predispose animals to developing cataracts.

If you suspect that your pet has gone blind, it is important to seek veterinary attention as soon as possible.

It is useful for your veterinarian to know whether you have observed a change in the appearance of the eyes, any changes in the overall health of your pet, and any recent medications they have been on, as well as any changes you have noted in their behaviour.

Your veterinarian will conduct a physical examination and may perform additional tests, such as blood tests and blood pressure measurement.

Your pet may be referred to a veterinary ophthalmologist for further evaluation and treatment.

In some cases, blindness can be reversed with treatment.

For example, it is possible for detached retinas to be surgically reattached. Similarly, cataracts may be removed.

My late dog Phil was almost entirely blind when cataract surgery restored his vision.

Interestingly, the first thing he did with his brand new eyes was walk up to the cat's food bowl and pee in it, as if he had been waiting for the opportunity to do so for some time.

Because some conditions must be treated in a narrow window of time to ensure vision can be restored, it is important to see your veterinarian early if you suspect that your pet's vision has deteriorated.

Dogs and cats can adapt well to loss of vision over time, with most able to successfully navigate their way around their home.

If you do live with a blind or vision-impaired dog or cat, there are a number of steps that you can take to make life easier for them:

BIONDI, V., PUGLIESE, M., VOSLAROVA, E., LANDI, A. & PASSANTINO, A. 2022. Animal Welfare Considerations and Ethical Dilemmas Inherent in the Euthanasia of Blind Canine Patients. Animals, 12. DOI: 10.3390/ani12070913

Dr Anne Quain BVSc (Hons), MANZCVS (Animal Welfare), Dip ECAWBM (AWSEL)is a lecturer at the Sydney School of Veterinary Science and a practising veterinarian.

More:
Lifting the lid on eye health and sight loss in your pets - Daily Liberal

Equities analysts expect LianBio (NASDAQ:LIAN Get Rating) to announce earnings per share (EPS) of ($0.26) for the current fiscal quarter, according to Zacks Investment Research. Zero analysts have provided estimates for LianBios earnings, with the highest EPS estimate coming in at ($0.22) and the lowest estimate coming in at ($0.31). The firm is expected to issue its next earnings report on Monday, January 1st.

According to Zacks, analysts expect that LianBio will report full-year earnings of ($1.32) per share for the current fiscal year, with EPS estimates ranging from ($1.65) to ($1.07). For the next year, analysts expect that the business will report earnings of ($1.73) per share, with EPS estimates ranging from ($2.20) to ($1.44). Zacks Investment Researchs EPS averages are an average based on a survey of sell-side research analysts that that provide coverage for LianBio.

LianBio (NASDAQ:LIAN Get Rating) last posted its earnings results on Wednesday, March 30th. The company reported ($0.28) earnings per share (EPS) for the quarter, beating analysts consensus estimates of ($0.72) by $0.44.

Several institutional investors have recently modified their holdings of LIAN. Victory Capital Management Inc. acquired a new stake in LianBio during the 4th quarter worth $1,069,000. Bank of America Corp DE acquired a new stake in LianBio during the 4th quarter worth $519,000. Alps Advisors Inc. acquired a new stake in LianBio during the 4th quarter worth $750,000. Element Capital Management LLC acquired a new stake in LianBio during the 4th quarter worth $124,000. Finally, TD Asset Management Inc. acquired a new position in shares of LianBio in the 4th quarter valued at $954,000. 62.99% of the stock is owned by institutional investors and hedge funds.

Shares of LianBio stock traded down $0.26 during midday trading on Thursday, reaching $4.91. The company had a trading volume of 435,320 shares, compared to its average volume of 411,834. The companys fifty day moving average is $4.19. LianBio has a 1-year low of $2.61 and a 1-year high of $16.37.

About LianBio (Get Rating)

Lianbio, a biopharmaceutical company, engages in developing and commercializing medicines for cardiovascular, oncology, respiratory, opthalmology, and inflammatory diseases in China and other Asian countries. The company develops mavacamten for the treatment of obstructive and non-obstructive hypertrophic cardiomyopathy, and heart failure with preserved ejection fraction; TP-03 for the treatment of Demodex blepharitis; NBTXR3 for the treatment of head and neck squamous cell carcinoma, and solid tumor IO combinations; Infigratinib for the treatment of second-line and first-line cholangiocarcinoma, and gastric and other cancers; BBP-398 for solid tumors; Omilancor for ulcerative and Crohn's disease; NH-13 for ulcerative colitis; LYR-210 for chronic rhinosinusitis; and Sisunatovir for respiratory syncytical virus.

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LianBio (NASDAQ:LIAN) Expected to Post Earnings of -$0.26 Per Share - Defense World

Scientists from the United Kingdom have analyzed the full genetic blueprints of more than 18,000 cancer samples, finding new patterns of mutations that could help doctors provide better, more personalized treatment

By LAURA UNGAR AP Science Writer

April 21, 2022, 6:02 PM

3 min read

Scientists have analyzed the full genetic blueprints of more than 18,000 cancer samples, finding new patterns of mutations that could help doctors provide better, more personalized treatment.

Their study, published Thursday in the journal Science, isnt the first to do such comprehensive whole genome analyses of cancer samples. But no one has ever done so many.

This is the largest cohort in the world. It is extraordinary, said Serena Nik-Zainal of the University of Cambridge, who was part of the team.

Just over 12,200 surgical specimens came from patients recruited from the U.K. National Health Service as part of a project to study whole genomes from people with common cancers and rare diseases. The rest came from existing cancer data sets.

Researchers were able to analyze such a large number because of the same improvements in genetic sequencing technology that recently allowed scientists to finally finish decoding the entire human genome more capable, accurate machines.

We can really begin to tease out the underpinnings of the erosive sort of forces that go to sort of generate cancer," said Andrew Futreal, a genomic medicine expert at MD Anderson Cancer Center in Houston who was not involved in the study.

Cancer is a disease of the genome, or full set of instructions for running cells, that occurs when changes in a persons DNA cause cells to grow and divide uncontrollably. In 2020, there were about 19 million new cancer cases worldwide.

For the study, researchers looked at 19 different types breast, colorectal, prostate, brain and others and identified 58 new clues to the causes of cancer called mutational signatures" that contribute to the development of the disease. They also confirmed 51 of more than 70 previously reported mutation patterns, Nik-Zainal said.

Some arise because of problems within a persons cells; others are sparked by environmental exposures such as ultraviolet radiation, tobacco smoke or chemicals.

Knowing more of them helps us to understand each persons cancer more precisely, which can help guide treatment, Nik-Zainal said.

Genetic sequencing is already being woven into cancer care as part of the growing trend of personalized medicine, or care based on a patients genes and specific disease. Now doctors will have much more information to draw from when they look at individual cancers.

To help doctors use this information, researchers developed a computer algorithm that will allow them to find common mutation patterns and seek out rare ones. Based on a particular pattern, Nik-Zainal said a doctor may suggest a certain course of action, such as getting immunotherapy.

Futreal said the data can also show doctors what tends to happen over time when a patient develops a cancer with a certain mutation pattern helping them intervene earlier and hopefully stop the developing disease in its tracks.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institutes Department of Science Education. The AP is solely responsible for all content.

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Study mines cancer genetics to help with targeted treatment - ABC News

Pregnancy for women marks the beginning of a new stage in their lives. Like any other parent, Juhi (namechanged) was excited when she learned about her pregnancy. She had suffered a miscarriage previouslyas her foetus was affected by down syndrome. While consulting with a geneticist, she was advised of a few options that included a non-invasive prenatal test (NIPT) to help screen for down syndrome and a fewother chromosomal disorders. She chose NIPT and waited anxiously for the results. The results arrived soon enough, and it was observed that Juhis baby had a very low or negligible risk ofhaving a serious chromosomal disorder. A few months later she delivered a healthy baby girl. Juhi was elated with the outcome and also understood the value of a genetic test and now advises all herrelatives to undergo a prenatal screening test. A non-invasive prenatal screening test provides expecting parents with reliable information about theirbabys genetic makeup. Such information is vital to expectant parents for thought-through earlypregnancy decisions and to avoid the distress caused by the birth of an abnormal baby unexpectedly.

What are chromosomaldisorders?

The human genetic material consists of 23 pairs of chromosomes. Therefore, any change in this number,wherein extra gain or loss of chromosome can lead to a serious disorder. The most common of thesedisorders are, Trisomy 21, Trisomy 18 and Trisomy 13, in the population.The estimated risk incidence of a baby with a chromosomal disorder is 1:166 births.Therefore, standard pregnancy care involves early screening for serious chromosomal abnormalities.

Genetic screening tests allow for identifying the genetic disorders or potential risks that the unborn babymay carry.NIPT (Non-Invasive Prenatal Test) has brought precision to the practice of diagnosis. With the advancement in technology, tests have been developed that are safe for the foetus and non-invasive. The non-invasive prenatal screening test can screen for common chromosomal abnormalitiessuch as Trisomy 21(Down syndrome), Trisomy 18 (Edward syndrome), Trisomy 13 (Patau syndrome) andcertain other abnormalities like monosomy X (Turners syndrome). There are three main reasons why couples should opt for a test:

It helps identify foetuses at risk of serious chromosomal abnormality.

Leads to better management by providing early information.

Prepares for birth and early intervention wherever possible.

Who needs to get tested?

Non-invasive prenatal testing can be recommended to any pregnant woman but is usually recommendedwhen:

The woman is above 30 years of age. Maternal serum screening provides abnormal results.

Certain abnormalities during the ultrasound are identified.

There is a family history of chromosomal conditions or congenital disabilities.

Couples have had a child with a chromosomal disorder.

A couple has a history of infertility or pregnancy loss.

Genetic testing of the pregnancy remains important as pregnancy is a time-sensitive period. When the general pregnant population is screened, most pregnancies eventually have a low risk of theseconditions. However, about 2-3% of the tested population by NIPT, receive a highrisk result whichrequires follow up confirmatory testing through invasive procedures.

(The author is an expert atreproductive genomics.)

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It's in the genetics - Deccan Herald

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Genetic, clinic and histopathologic characterization of BRCA-associated hereditary breast and ovarian cancer in southwestern Finland | Scientific...

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If we understand the causes of cancer, then we can start highlighting the known causes, the lifestyle issues that introduce or increase our risk

Environmental and metabolic factors not just genetics are growing considerations in the fight against cancer, concludes a research review by a leading expert at the University of Alberta.

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Cancer as a genetic disease, focusing on the set of genetic instructions every person is born with; it is also an environmental disease, focusing on the exposome, which includes everything a persons body has been exposed to; and cancer is a metabolic disease, focusing on the metabolome, or all the chemical byproducts of the process of metabolism, explains David Wishart, professor in the departments of biological sciences and computing science, in a Thursday news release.

But that metabolic perspective hasnt had much research until now, as more scientists begin to understand the metabolomes role in cancer.

Heritable cancers account for just five to 10 per cent of all cancers, Wishart said, with the other 90 to 95 per cent initiated by factors in the exposome, which in turn trigger genetic mutations.

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Thats an important thing to consider, because it says that cancer isnt inevitable.

As cancer develops and spreads in the body, it creates its own environment and introduces certain metabolites, becoming a self-fuelled disease. And thats where cancer as a metabolic disorder becomes really important.

Considering the genome, exposome and metabolome together when thinking about cancer shows more promise for finding treatments.

Researchers who focus only on the genetic perspective are looking to address particular mutations but there are around 1,000 genes that can become cancerous when mutated, and it typically takes two different mutations within these cells for cancer to grow, notes Wishart, meaning there are a million potential mutation pairs. Then it can become hopeless to narrow down possibilities when seeking new treatments.

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But considering cancer from the metabolic perspective, there are just four major metabolic types, said Wishart, so determining the patients cancer type can immediately guide doctors on the best treatment for their specific cancer.

It really doesnt make a difference where the cancer is its something youve got to get rid of. Its how it thrives or grows that matters, said Wishart. It becomes a question of, Whats the fuel that powers this engine?

Wishart cautions that health-care providers still need a mix of therapeutics for cancer, and a deeper understanding of the metabolome and its role in the cancer feedback loop is also critical to preventing cancer.

If we understand the causes of cancer, then we can start highlighting the known causes, the lifestyle issues that introduce or increase our risk, he said.

From the prevention side, changing our metabolism through lifestyle adjustments will make a huge difference in the incidence of cancer.

The research review was funded by Genome Canada, the Canadian Institutes of Health Research and the Canada Foundation for Innovation.

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Treating, preventing cancer beyond genetics: U of A researcher - Edmonton Journal

Photo provided by Lionheart Cannabis

Chris Fanuzzi calls it his genetic library.

Seed descriptions, batch logistics and references to growers and cultivators who supplied some of the seeds are all noted in the heaps of pages of mostly handwritten notes in his trusty binder.

There are more than 400 recipes for Fanuzzis renowned rotating cannabis menu items, including the famous original Montana Silvertip, a hybrid strain. In the cannabis industry, the term strain refers to a variety of the cannabis plant and can include characteristics such as chemical profile, appearance and effects on consumers.

Maintaining the integrity of the original seeds over time is incredibly difficult for any cultivator, said Fanuzzi, owner and founder of Lionheart Cannabis, Montanas leading medical and recreational cannabis provider. Its an art to be able to sustain a particular genetic makeup of any one plant, especially when you consider these plants are growing alongside one another with the ability to pick up characteristics of the plant strains located, literally, right next to them. And that doesnt even take into account trying to maintain a completely stable environment from year to year, all against a backdrop of legislation that is constantly changing.

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But Fanuzzi has made it work. His company is renowned for its focus on quality, top-of-the-line products, compassionate patient care and educational awareness among clients.

Lionheart currently produces myriad oils, edibles and tinctures in a variety of flavors, strengths and price ranges. In addition to its headquarters in Bozeman, the company has five cultivation facilities throughout the state, as well as dispensaries in Billings, Butte, Helena, Great Falls (Herbal Bliss), Kalispell, Livingston andMissoula.

With 50 to 60 strains on the shelves at any one time, Lionheart is set to roll out scrolling digital menus that will provide customers with real-time product availability and pricing. The company is also enhancing its on-site customer experience by redesigning retail space to include more open floor plans and visual product display areas.

We want to encourage our customers to spend as much time as they want with our budtenders when they are onsite, to look at every jar to find that bud that is really going to work for them, he said. The online menu will only complement that experience.

But back to Montana Silvertip. A genetic cross between Purple Urkel (also known as Granddaddy Purple) and Super Silver Haze, the sativa-dominant bud has a THC level anywhere from 20% to 30%, with an earthy pine and blueberry taste.

Its an absolutely beautiful strain with hues of bright lavender and frosty white, Fanuzzi said. We continue to cross-pollinate its seeds with some of our other renowned strains such as Wedding Crasher, Mandarin Cookie, Purple Punch and Meathead, resulting in some really incredibly viable genetics with lots of different properties that are very popular with our customers.

Other favored staff picks include Do Si Dos, Kimbo Kush, Blue Dream, Lucky Charms, Key Lime Pie and Ginger Tea. And while consumers should note the THC potency levels listed on the product packaging, Fanuzzi said other things to consider include terpene profiles, how the buds are stored (glass jars and turkey bags are best), the smell (too much moisture results in a moldy odor) and feel (should feel spongy like a marshmallow when squeezed). If the bud is too dry, it will crumble. Also, buds stored in sunlight lose their potency more quickly.

Fanuzzi said as his recipe library for strains continues to grow, it also includes notations for those strains that have been bred out over time, including one of his most legendary" strains, the Papaya. Unfortunately, I developed it back in 2007 and never cloned it. So once it was gone, it was gone, recalled Fanuzzi.

Strains today represent combinations and cross-breeding of some of the best products and varieties people like. There are only so many families of land-raised genetics out there, so you continue to fine-tune until you achieve what you think is the perfect combination.

At that point, Fanuzzi adds another page to his binder.

Visit lionheartcannabis.com for more information.

Information provided is for educational and informational purposes only and does not supersede any medical advice given by a physician. Cannabis is still considered a schedule 1 controlled substance and is illegal under federal law. Adults who consume cannabis must keep cannabis products away from animals and out of reach of children. Note that the intoxicating effects of cannabis can sometimes be delayed, so do not operate a vehicle or machinery after consumption. Use of cannabis during pregnancy or while breastfeeding may be harmful. By purchasing cannabis from a dispensary, you are assuming the risk of any damage or loss that occurs during its use.

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Lionheart Cannabis' genetic strains stand the test of time - Billings Gazette

Is it possible to breed low-emissioncattle and sheep?

A group of Australian researchers and industry leaders think so and they are putting $19 million towards making it happen.

The University of New England, Armidale (UNE) is collaborating with Angus Australia, Meat and Livestock Australia and the NSW Department of Primary Industry to develop genetics to breed livestock that emits less methane.

The project is in line with the beef industry's goal to reach zero carbon emissions by 2030.

"We have always been keen to look at measuring the traits related to methane emissions on our cattle so in the future we can select Angus bulls that will produce lower methane but still be productive," Angus Australia's general manager for genetic improvementChristian Duffsaid.

Mr Duff said the organisation's involvement in the project was driven by the consumer.

"There is no doubt there is a trend towards people wanting to be aware of where their product comes from and its impact on the environment.

"The way we can have an impact is by making sure we're recording those methane traits on cattle ... and then in the future having information to select bulls."

UNE researchersare confident that, through the project, they can achieve a steady and permanent reduction in methane emissions from livestock.

Two UNEprofessors will investigate how to improve the genetic make-up of sheep and cattle.

Over the next five years, they will measure the methane output of 8,000 cattle and 10,000 sheep living in both feedlot and grazing conditions.

The variation between different animals will be analysed and data used to predict which of those animals have genetics that may lower the emissions they produce.

Associate Professor Sam Clark willresearchthe beef component, and saidboth projects could result in a 25 per cent reduction in methane emissions in livestock by 2050.

"A plausible amount to expect from genetic technologies is about 1 per cent methane reduction per year,"he said.

"The key point about that 1 per cent per year is that, when we use breeding to make that change, it's cumulative and permanent.

"It's a bit like your interest rate for the bank, it just keeps accumulating on top of itself."

The project is scheduled to start laterthis month.

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Armidale researchers hope genetic selection will be key to raising steaks with lower emissions - ABC News

About the position

There is a vacancy for one PhD candidate at The Department of Clinical and Molecular Medicine in collaboration with The Department of Medical Genetics at St. Olavs hospital. The PhD candidate will work on different aspects of the Clinical Academic Group for Rare Genetic Diseases (CAG).

One of the main aims of the CAG is to apply state-of-the-art disease-modelling to the rare genetic diseases. The PhD project will address the steps in onset of neurodevelopmental diseases and identify potential points for diagnostic and therapeutic intervention.

We have implemented different human cell culture and organoid models that enable studying of disease development and progression, as well as the analysis of relevant pathomechanisms. The PhD student will be involved in generation and characterization of patient-specific and healthy-individual induced pluripotent stem cells, development of disease models and their characterization through transcriptome and proteome analysis, imaging and functional testing. As such the project includes work with big data sets.

Required selection criteria

The appointment is to be made in accordance with the regulations in force concerningState Employees and Civil ServantsandRegulations concerning the degrees ofPhilosophiaeDoctor (PhD)andPhilosodophiaeDoctor (PhD) in artistic researchnational guidelines for appointment as PhD, post doctor and research assistant

Preferred selection criteria

Personal characteristics

We offer

Salary and conditions

PhD candidates are remunerated in code 1017, and are normally remunerated at gross from NOK 491 200 per annum before tax, depending on qualifications and seniority. From the salary, 2% is deducted as a contribution to the Norwegian Public Service Pension Fund.

The period of employment is 3 years.

Appointment to a PhD position requires that you are admitted to thePhD programme in Medicine and Health Sciences within three months of employment, and that you participate in an organized PhD programme during the employment period.

The engagement is to be made in accordance with the regulations in force concerning State Employees and Civil Servants, and the acts relating to Control of the Export of Strategic Goods, Services and Technology. Candidates who by assessment of the application and attachment are seen to conflict with the criteria in the latter law will be prohibited from recruitment to NTNU. After the appointment you must assume that there may be changes in the area of work.

It is a prerequisite you can be present at and accessible to the institution daily.

About the application

The application and supporting documentation to be used as the basis for the assessment must be in English.

Publications and other scientific work must follow the application. Please note that applications are only evaluated based on the information available on the application deadline. You should ensure that your application shows clearly how your skills and experience meet the criteria which are set out above.

The application must include:

If all,or parts,of your education has been taken abroad, we also ask you to attach documentation of the scope and quality of your entire education, both bachelor's and master's education, in addition to other higher education. Description of the documentation required can befoundhere. If you already have a statement fromNOKUT,pleaseattachthisas well.

Joint works will be considered. If it is difficult to identify your contribution to joint works, you must attach a brief description of your participation.

In the evaluation of which candidate is best qualified, emphasis will be placed on education,experienceand personal and interpersonalqualities.Motivation,ambitions,and potential will also countin the assessment ofthe candidates.

NTNU is committed to following evaluation criteria for research quality according toThe San Francisco Declaration on Research Assessment - DORA.

General information

Working at NTNU

A good work environment is characterized by diversity. We encourage qualified candidates to apply, regardless of their gender, functional capacity or cultural background.

The city of Trondheimis a modern European city with a rich cultural scene. Trondheim is the innovation capital of Norway with a population of 200,000. The Norwegian welfare state, including healthcare, schools, kindergartens and overall equality, is probably the best of its kind in the world. Professional subsidized day-care for children is easily available. Furthermore, Trondheim offers great opportunities for education (including international schools) and possibilities to enjoy nature, culture and family life and has low crime rates and clean air quality.

As an employeeatNTNU, you must at all times adhere to the changes that the development in the subject entails and the organizational changes that are adopted.

In accordance with The Public Information Act (Offentleglova), your name, age, position and municipality may be made public even if you have requested not to have your name entered on the list of applicants.

If you have any questions about the position, please contact Professor Barbara van Loon, telephone +47 73 59 84 23, emailbarbara.v.loon@ntnu.no; Senior consultant clinical geneticist Rune stern, emailRune.Ostern@stolav.no. If you have any questions about the recruitment process, please contact Vebjrn F. Andreassen, e-mail:vebjorn.andreassen@ntnu.no

Please submit your application electronically via jobbnorge.no with your CV, diplomas and certificates. Applications submitted elsewhere will not be considered. Diploma Supplement is required to attach for European Master Diplomas outside Norway. Chinese applicants are required to provide confirmation of Master Diploma fromChina Credentials Verification (CHSI).

Application deadline: 16.05.22

NTNU - knowledge for a better world

The Norwegian University of Science and Technology (NTNU) creates knowledge for a better world and solutions that can change everyday life.

The Department of Clinical and Molecular Medicine (IKOM):

The Department of Clinical and Molecular Medicine (IKOM) is NTNUs largest department, with 450 employees. Our research and teaching help to improve treatment and health.

IKOM has expertise in basic, clinical and translational research within broad disciplinary areas. We study childrens and womens health, cancers, blood disorders and infectious diseases, gastroenterology, inflammation, metabolic disorders, laboratory sciences and medical ethics. The Department offers teaching in medicine at masters and PhD level. We also offer continuing education for employees in the health services.

Deadline16th May 2022EmployerNTNU - Norwegian University of Science and TechnologyMunicipalityTrondheimScopeFulltimeDurationProjectPlace of service

Excerpt from:
PhD Candidate in Rare Genetic Diseases job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 291220 - Times Higher Education

Daewoong Pharmaceutical and HanAll Biopharma invest in the broad potential of Turn Biotechnologies

Turn has developed a novel cell rejuvenating platform with significant potential for application in an array of age-related diseases

SEOUL, South Korea, April 11, 2022 /PRNewswire/ -- Daewoong Pharmaceutical (KRX: 069620.KS) and HanAll Biopharma (KRX: 009420.KS) today announced expansion of their open collaboration strategy by investing in Turn Biotechnologies, a Silicon Valley based company focused on developing novel mRNA medicines. The companies are supporting Turn Bio's continued development of a high-potential platform and are considering future long-term collaborations.

Turn Bio is a pre-clinical-stage biopharmaceutical company focused on cellular repair via epigenetic reprogramming of cells. The technological foundation for Turn Bio's proprietary Epigenetic Reprogramming of Age (ERA) methodology was developed by Turn Bio's co-founders in the Sebastiano Lab, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine. The technology has since been patented and Turn Bio is currently using it to complete pre-clinical research on therapies targeting indications in dermatology and immunology, as well as developing therapies for ophthalmology, osteoarthritis and the muscular system.

"Many age-related diseases have long been significant areas of patients' unmet need," said Dr. Almira Chabi, chief medical officer and chief development officer at HanAll Pharmaceutical International. "Turn Bio's innovative platform may bring a pivotal transformation to a wide array of therapeutic areas. HanAll is committing support and investment to help realize the full potential of this pioneering technology as Turn Bio advances to a new phase of growth."

"The support of Daewoong Pharmaceutical and HanAll Biopharma validates our approach to cellular rejuvenation and enables Turn to expand its efforts in multiple therapeutic indications," said Anja Krammer, the company's CEO. "We are thrilled that a company as well known for its innovation, has taken interest in our promise to transform the way medicine treats diseases of aging and we look forward to further collaborations to help change quality of life and healthcare economics globally."

Story continues

The proceeds from this round of financing will support Turn Bio's advancement towards a phase 1 trial of its mRNA therapy candidate TRN-001, which targets indications in dermatology.

About HanAll Biopharma Co., Ltd.

HanAll Biopharma (KRX: 009420.KS) is a global biopharmaceutical company founded in 1973, with a mission of making meaningful contributions to patients' lives by introducing innovative, impactful therapies to address severe unmet medical needs. HanAll has been operating a portfolio of pharmaceutical products in areas ranging from endocrine, circulatory, and urologic diseases for more than 48 years.

HanAll has also expanded its focus to ophthalmology, immunology, oncology and neurology to discover and develop innovative medicines for patients with diseases for which there are no effective treatments. A leading pipeline asset, HL161 (INN: batoclimab), an anti-FcRn antibody drug, is in Phase 3 and Phase 2 trials across the world for the treatment of rare autoimmune disorders including myasthenia gravis, thyroid eye disease, warm autoimmune hymolytic anemia, neuromyelitis optica, and immune thrombocytopenia. Another main asset, HL036 (INN: tanfanercept), an anti-TNF alpha protein drug, is in Phase 3 clinical trials in the US and China for the treatment of dry eye disease.

For further information visit our website, and connect with us on linkedin. For any media inquiries, please contact HanAll PR/IR (pr@hanall.com, ir@hanall.com).

About Daewoong Pharmaceutical. Co., Ltd. (https://www.daewoong.co.kr/en)

Established in 1945, Daewoong Pharmaceutical Co., Ltd. is a leading South Korean pharmaceutical company that develops, manufactures, and commercializes pharmaceuticals for both domestic and international markets. With a strong and innovative in-house R&D and advanced manufacturing facilities, Daewoong provides a total healthcare solution to customers across the globe. Continuing on its course of building a strong global healthcare company, Daewoong has broadened international operations by establishing branch offices and research centers throughout Asia and the United States. Daewoong has also expanded strategic partnerships in more than 100 countries worldwide.

About Turn Biotechnologies

Turn Bio is a pre-clinical-stage company focused on repairing tissue at the cellular level. The company's proprietary mRNA platform technology, ERA, restores optimal gene expression by combatting the effects of aging in the epigenome. This restores the cells' ability to prevent or treat disease, and heal or regenerate tissue and will help to fight incurable chronic diseases.

Turn Bio's technology provides a platform from which to attack a variety of now incurable chronic diseases. The company is currently completing pre-clinical research on tailored therapies targeting indications in dermatology and immunology, as well as developing therapies for ophthalmology, osteo-arthritis and the muscular system. For more information, see turn.bio or contact Jim Martinez, rightstorygroup / jim@rightstorygroup.com or (312) 543-9026.

Disclaimer statement

The contents of this announcement include statements that are, or may be deemed to be, "forward-looking statements." These forward-looking statements can be identified by the use of forward-looking terminology, including the terms "believes," "estimates," "anticipates," "expects," "intends," "may," "will," or "should" and include statements HANALL (the company, we) makes concerning its 2022 business and financial outlook and related plans; the therapeutic potential of its product candidates; the intended results of its strategy and the company, and its collaboration partners', advancement of, and anticipated clinical development, data readouts and regulatory milestones and plans, including the timing of planned clinical trials and expected data readouts; the design of future clinical trials and the timing and outcome of regulatory filings and regulatory approvals. By their nature, forward-looking statements involve risks and uncertainties, and readers are cautioned that any such forward-looking statements are not guarantees of future performance. The company's actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors our expectations regarding its the inherent uncertainties associated with competitive developments, preclinical and clinical trial and product development activities and regulatory approval requirements; our reliance on collaborations with third parties; estimating the commercial potential of our product candidates; our ability to obtain and maintain protection of intellectual property for its technologies and drugs; our limited operating history; and our ability to obtain additional funding for operations and to complete the development and commercialization of its product candidates. A further list and description of these risks, uncertainties and other risks can be found in Korea Stock Exchange (KRX) filings and reports, including in our most recent annual report as well as subsequent filings and reports filed by the company with the KRX. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. We undertake no obligation to publicly update or revise the information in this press release, including any forward-looking statements, except as may be required by Korean law and regulations.

Cision

View original content:https://www.prnewswire.com/news-releases/daewoong-pharmaceutical-and-hanall-biopharma-invest-in-turn-biotechnologies-to-expand-growth-initiative-301522583.html

SOURCE Daewoong Pharmaceutical and HanAll Biopharma

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Daewoong Pharmaceutical and HanAll Biopharma Invest in Turn Biotechnologies to Expand Growth Initiative - Yahoo Finance

Andrea Williams, chief executive of Christian Concern, said: Whatever is announced by the Government in May, the problems remain: the definitions are inadequate, human rights will be breached and there is no evidence that a ban will help anyone.

In such a scenario we will face no alternative but to pursue legal action against any proposed legislation in this area.

Ms Williams added: The Government is being strong-armed by manipulative campaigns rather than following its own research that further legislation is not needed.

The fear of upsetting privileged lobbyists runs so deep the Prime Minister capitulated within hours.

No one has produced any evidence of what LGBT activists call coercive conversion therapy. What the activists describe would already be illegal.

The Governments proposals would only stop people seeking the change they want to see in their lives. That is a basic freedom which the Government should not try to take away.

Last week the Government was forced to cancel its first ever LGBT+ conference after more than 100 activist groups quit over its U-turn on conversion therapy.

As a result of the Government reiterating its commitment to excluding transgender people from the conversion therapy ban, a number of leading charities and organisations pulled out of the inaugural and international event, called Safe To Be Me.

It was set to take place in London from June 29 to July 1, coinciding with the 50th anniversary of the first official London Pride marches.

Christian Concern has threatened, if the Government does go ahead with any of its proposals as part of the Queens Speech on May 10, to bring legal proceedings on grounds of infringement upon rights of religious freedom enshrined in the European Convention on Human Rights.

A spokesman for Stonewall, one of the groups which pulled out of the Governments now collapsed Safe To Be Me conference, said: From the British Medical Association and NHS England to the UK Council for Psychotherapy and the Royal Colleges of GPs and Psychiatrists, medical and psychiatric expertise is in agreement: conversion practices do not work, can cause lifelong trauma and must be banned.

With half of conversion practices happening in religious settings, LGBTQ+ people of faith make up one of the largest groups of victims. Thats why were heartened that numerous religious leaders, including the former Archbishop of Canterbury, Rowan Williams, recently wrote to the Prime Minister in support of a ban.

We must continue to look to religious leaders who, rather than turn a blind eye to abuse, wish to address the harms done to other people who deeply hold and value their religious beliefs and community.

Read the original here:

Christian group prepares legal challenge over conversion therapy ban - The Telegraph

Bank of America (BAC) was the latest major bank to issue a recession shock warning two weeks after the Treasury yield curve inverted. Economists at the Bank of America expect inflation to worsen as the Russia-Ukraine war drags out, while the interest rate shock is just beginning to set in. Because the Fed is expected to remain aggressively hawkish for the foreseeable future to control the 40-year-high inflation rates, the U.S. is currently on recession watch.

Thanks to the inelastic demand for healthcare products, investing in healthcare stocks can hedge some of the markets risks. Furthermore, only 66.4% of the total population have received at least one COVID-19 vaccine dose. As economies collectively push to accelerate the global vaccination drive, healthcare companies with COVID-19 vaccines in their portfolios are expected to benefit from the robust global demand.

Given this backdrop, we believe fundamentally strong healthcare companies Pfizer Inc. (PFE), Johnson & Johnson (JNJ), AbbVie Inc. (ABBV), Eli Lilly and Company (LLY), and Merck & Co., Inc. (MRK) are expected to grow substantially even during a recession. Thus, investing in these stocks now could hedge ones portfolio against the forthcoming potential recession.

Click here to checkout our Healthcare Sector Report for 2022

Pfizer Inc. (PFE)

New York City-based PFE specializes in biopharmaceutical products globally. Its portfolio includes medicines and vaccines served to wholesalers, retailers, healthcare providers, government agencies, pharmacies, and local communities.

On April 4, PFE agreed to acquire ReViral for up to $525 million. With this acquisition, the company would strengthen its capabilities in treating RSV disease and expand its anti-infective pipeline further.

On March 29, the FDA expanded emergency use authorization of COVID-19 vaccine booster in adults aged 50 years and older and authorized a second booster dose for individuals 12 years of age and older who have received the first shot. The second booster dose offers increased protection against severe disease and hospitalization.

Also last month, PFE announced positive results from a yearlong phase 3 trial of etrasimod, which is expected to be a best-in-class therapy in treating ulcerative colitis (UC).

PFEs revenue increased 105% year-over-year to $23.84 billion in its fiscal fourth quarter (ended December 31). Its net income grew 300.6% from its year-ago value to $3.39 billion, while its income from continuing operations improved 464.4% year-over-year to $3.58 billion over the period. The companys non-GAAP EPS increased 151.2% from the year-ago value to $1.08.

The $1.57 consensus EPS estimate for its fiscal first quarter (ended March 31, 2022) represents a 68.3% improvement year-over-year. The $24.55 billion consensus revenue estimate for the to-be-reported quarter indicates a 68.4% increase from the same period last year. The company has an excellent earnings surprise history; it surpassed the consensus EPS estimates in each of the trailing four quarters.

Over the past year, the stock has gained 50.7% in price to close its last trading day at $55.17.

PFEs POWR Ratings reflect this promising outlook. The company has an overall A rating, which translates to Strong Buy in our proprietary rating system. The POWR Ratings assess stocks by 118 distinct factors, each with its own weighting.

It has a B grade for Value, Growth, and Quality. Among the 174 stocks in the Medical Pharmaceuticals industry, it is ranked #14. Click here to see the additional POWR ratings of PFE for Momentum, Sentiment, and Stability.

Johnson & Johnson (JNJ)

JNJ in New Brunswick, N.J., is engaged in the research and development, manufacturing, and selling of healthcare products that are primarily focused on human health and well-being. The company operates through three segments: Consumer; Pharmaceutical; and Medical Devices. It offers its products to the public, retail outlets and distributors, wholesalers, hospitals, and healthcare professionals.

On March 14, JNJ was named in Fortune Worlds Most Admired Companies list for the 20th consecutive year. In addition, it was also ranked #1 on the Pharmaceutical Industry list for the ninth year in a row. These honors are indicative of JNJs unwavering commitment and strong performance within the industry.

On January 6, JNJ announced that based on the largest study in the U.S., a single shot of the JNJ vaccine demonstrated long-lasting protection for up to six months against COVID-19 breakthrough infections, hospitalizations, and ICU admissions. Given the resurgence of COVID-19 cases of late, the vaccine is expected to remain in demand globally.

On December 30, the company announced that the booster shot of the JNJ COVID-19 vaccine reduced the risk of hospitalization among healthcare workers in South Africa when Omicron was dominant, representing 85% of effectiveness.

During its fiscal 2021 fourth quarter (ended Dec. 31, 2021), JNJs net sales increased 10.4% year-over-year to $24.8 billion. Its gross profit rose 14.9% from its year-ago value to $16.85 billion. Its non-GAAP net earnings grew 14.4% from the same period last year to $5.68 billion, while its adjusted EPS came in at $2.13, representing a 14.5% increase year-over-year.

Analysts expect JNJs revenues to increase 6% year-over-year to $23.65 billion in the fiscal first quarter (ended March 31, 2022). Its EPS is expected to increase 0.4% to $2.60 in the about-to-be-reported quarter. It is no surprise that the company has surpassed the consensus EPS estimates in each of the trailing four quarters, which is excellent.

The stock has gained 13.2% in price over the past six months to close Fridays trading session at $182.12.

JNJs strong fundamentals are reflected in its POWR Ratings. The stock has an overall A rating, which equates to a Strong Buy in our POWR Ratings system. JNJ also has an A grade for Stability and a B grade for Value and Quality. The stock is ranked #5 of 174 stocks in the Medical Pharmaceuticals industry.

Click here to see the other ratings of JNJ for Growth, Sentiment, and Momentum.

AbbVie Inc. (ABBV)

ABBV is engaged in research and development, manufacturing, commercialization, and global sale of medicines and therapies. The North Chicago, Ill.-based concern offers its products in various categories: immunology, oncology, neuroscience, eye care, and womens healthcare. The company markets its products to wholesalers, distributors, government agencies, health care facilities, and independent retailers.

On April 5, ABBVs subsidiary, Allergan, announced positive results from its Phase 3 VIRGO trial evaluating twice-daily administration of VUITY (pilocarpine HCl ophthalmic solution) 1.25% in adults with presbyopia. The successful trials should strengthen the role of VUITY in treating patients with blurry near vision.

On March 17, the company received Health Canadas approval of SKYRIZI to treat adults with active psoriatic arthritis. This approval should accelerate the expansion of ABBVs immunology portfolio in Canada.

On March 15, ABBV and Scripps research collaborated to develop oral antiviral treatments to combat the new variants of Covid-19.

ABBVs net revenues increased 7.4% year-over-year to $14.89 billion in the fourth quarter, ended Dec. 31, 2021. The companys non-GAAP net earnings increased 13.3% from the year-ago value to $5.92 billion, while its operating earnings grew 35.2% year-over-year to $5.07 billion. ABBVs adjusted EPS rose 13.4% from the prior-year quarter to $3.31.

Analysts expect ABBVs EPS and revenue to increase 6.3% and 5.2%, respectively, year-over-year to $3.14 and $13.61 billion in its fiscal first quarter, ended March 31, 2022. The company has an excellent earnings surprise history; it surpassed the consensus EPS estimates in each of the trailing four quarters.

Shares of ABBV have risen 62.7% in price over the past year to close Fridays trading session at $174.96.

ABBV has an overall A rating, which translates to a Strong Buy in our proprietary rating system. Also, it has a B grade for Sentiment and Quality. Also, it is ranked #8 in the Medical Pharmaceuticals industry.

In addition to the POWR Ratings grades I have just highlighted, one can see the ABBV ratings for Growth, Value, Momentum, and Stability here.

Eli Lilly and Company (LLY)

LLY is a drug manufacturing company. Its offerings include Basaglar, Humalog, Humulin, Jardiance, Trajenta, Erbitux, Retevmo, Tyvyt, Emgality, and Reyvow, among various others. The Indianapolis, Ind.-based company distributes its products in the U.S. and eight other countries.

On April 8, LLY delivered its first shipment of diabetes medicine to Ukraine amid the devastating war there. The company will make additional deliveries of medicines, including cancer treatments and COVID-19 treatments, to ease human suffering in that war.

On March 26, the company announced that adults with alopecia areata who took OLUMIANT 4-mg saw at least 90% scalp hair coverage at 52 Weeks in LLYs Pivotal Phase 3 Studies. With such remarkable results, OLUMIANT could become the first medicine ever approved to treat alopecia areata in 2022.

On January 13, the WHO recommended LLYs baricitinib, sold under the brand name Olumiant, in combination with corticosteroids, for patients with severe COVID-19. The drug has been observed to improve the survival rate and reduce the need for ventilation.

In the fourth quarter, ended Dec. 31, 2021, LLYs revenue increased 8% year-over-year to $8 billion. Its non-GAAP net income increased 8% from the year-ago value to $2.27 billion, while its non-GAAP EPS came in at $2.49, representing an 8% year-over-year improvement.

The $2.15 consensus EPS estimate for its fiscal first quarter (ended March 31, 2022) represents a 15.1% improvement year-over-year. The $7.04 billion consensus revenue estimate for the to-be-reported quarter represents a 3.4% increase from the same period last year.

LLY has gained 69% in price over the past year, closing Fridays trading session at $311.69.

The company has an overall A rating, which translates to Strong Buy in our proprietary rating system. It is no surprise that LLY has a B grade for Growth, Stability, Sentiment, and Quality. In the Medical Pharmaceuticals industry, it is ranked #10.

Beyond what we have stated above, we have also given LLY grades for Momentum and Value. Get all the LLY ratings here.

Merck & Co., Inc. (MRK)

MRK is a global provider of health solutions through its prescription medicines, vaccines, biological therapies, and animal health products. The Kenilworth, N.J.-based company operates through two segments: Pharmaceutical; and Animal Health. It offers its products to drug wholesalers and retailers, hospitals, government agencies, and other health care providers.

On April 4, MRK expanded its vaccines manufacturing facility in Elkton to increase the supply of the companys HPV vaccine and enable broad equitable access. With this expansion, MRK should help meet the growing global demand for vaccines.

On March 25, MRK received a positive opinion from EU CHMP for KEYTRUDA for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in five distinct types of cancer. This positive opinion reflects MRKs advancement in the development of cancer treatments.

On March 2, WHO recommended MRKs COVID-19 antiviral pill (molnupiravir), for high-risk patients, such as the immunocompromised, the unvaccinated, older people and those with chronic diseases.

During the fourth quarter, ended Dec. 31, 2021, MRKs net sales increased 24% year-over-year to $13.52 billion. The companys non-GAAP net income increased 84% year-over-year to $4.58 billion, while its non-GAAP EPS grew 84% from the prior-year quarter to $1.80.

Analysts expect MRKs revenues to increase 20.5% year-over-year to $14.56 billion in its fiscal first quarter (ended March 31, 2022). Its EPS is expected to increase 27.8% to $1.79 in the about-to-be-reported quarter. Shares of MRK have gained 20.4% in price over the past year.

MRKs strong fundamentals are reflected in its POWR Ratings. The stock has an overall A rating, which equates to Strong Buy in our proprietary rating system. MRK also has a B grade for Value, Growth, Sentiment, Quality, and Stability. The stock is ranked #2 in the Medical Pharmaceuticals industry.

In addition to the POWR Ratings I have just highlighted, click here to see the MRK ratings for Momentum.

Click here to checkout our Healthcare Sector Report for 2022

PFE shares were trading at $54.01 per share on Monday afternoon, down $1.16 (-2.10%). Year-to-date, PFE has declined -7.84%, versus a -6.71% rise in the benchmark S&P 500 index during the same period.

Shweta's profound interest in financial research and quantitative analysis led her to pursue a career as an investment analyst. She uses her knowledge to help retail investors make educated investment decisions. More...

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PFE: 5 Global Healthcare Stocks to Buy as BofA Warns of a - StockNews.com

REDWOOD CITY, Calif., April 06, 2022 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced that it has received feedback via a Type C meeting written response from the U.S. Food and Drug Administration (FDA) related to Adverums planned Phase 2 trial of ADVM-022 in wet age-related macular degeneration (wet AMD). Adverum requested the FDAs feedback to ensure alignment with the regulatory agency ahead of filing the Investigational New Drug (IND) amendment for the Phase 2 trial. The trial is designed to evaluate the 2 X 10^11 vg/eye dose and a new, lower 6 X 10^10 vg/eye dose of ADVM-022, along with new enhanced prophylactic steroid regimens, including local steroids and a combination of local and systemic steroids.

We are extremely pleased to have feedback from the FDA regarding our clinical development plan for a Phase 2 trial of ADVM-022 in wet AMD. We are looking forward to completing the IND amendment process by mid-2022 and remain on track to initiate our Phase 2 study in the third quarter of 2022, stated Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. ADVM-022 is a single, intravitreal injection gene therapy product that we believe has the potential to provide a durable and safe treatment option that addresses the needs of wet AMD patients, caregivers, retina specialists and health systems.

As an investigator in Adverums OPTIC trial, I am pleased to give my patients the option for a long-lasting, durable treatment for wet AMD, commented David S. Boyer, M.D., physician at Retina-Vitreous Associates Medical Group and member of Adverums Scientific Advisory Board. It is clear that newer long-acting anti-VEGF treatments are needed, especially one that reduces the burden of frequent anti-VEGF injections that many patients currently have to endure. The work that Adverum is doing to advance ADVM-022 as a treatment option is invaluable for patients and the field.

Expected Near-Term ADVM-022 Development Milestones

About Adverum Biotechnologies

Adverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs in serious ocular and rare diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of patients with neovascular or wet age-related macular degeneration. For more information, please visit http://www.adverum.com.

Forward-looking Statements

Statements contained in this press release regarding events or results that may occur in the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to: statements regarding Adverums plans to initiate a Phase 2 trial of ADVM-022 in wet AMD at the 2 X 10^11 vg/eye dose and a new, lower 6 X 10^10 vg/eye dose; and statements under the caption Expected Near-Term ADVM-022 Development Milestones. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverums novel technology, which makes it difficult to predict the time and cost of product candidate development and regulatory uncertainties; the results of early clinical trials not always being predictive of future results; the potential for future complications or side effects in connection with use of ADVM-022.Additional risks and uncertainties facing Adverum are set forth under the caption Risk Factors and elsewhere in Adverums Securities and Exchange Commission (SEC) filings and reports, including Adverums Annual Report on Form 10-K for the year ended December 31, 2021 filed with the SEC on March 29, 2022. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Inquiries

Anand ReddiVice President, Head of Corporate Strategy and External Affairs & Engagement Adverum Biotechnologies, Inc.T: 650-649-1358

Or

Investors:Laurence WattsGilmartin GroupT: 619-916-7620E: laurence@gilmartinir.com

Media:Jennifer ArcureCanale CommunicationsT: 917-603-0681E: Jennifer.Arcure@canalecomm.com

Source: Adverum Biotechnologies, Inc.

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Adverum Biotechnologies Proceeds with IND Amendment for ADVM-022 Phase 2 Trial in Wet AMD After Receiving Requested Type C Meeting Feedback from the...

MUNICH, Germany, April 06, 2022 (GLOBE NEWSWIRE) -- ViGeneron GmbH, a next-generation gene therapy company, today announced a target-specific strategic collaboration and option agreement with Regeneron Pharmaceuticals Inc. (Regeneron) to develop and commercialize a gene therapy product based on ViGenerons novel engineered recombinant adeno-associated virus vectors (vgAAVs) to treat an inherited retinal disease (IRD).

Under the terms of the research collaboration, Regeneron and ViGeneron will create and validate vgAAV-based therapeutic candidates for one undisclosed IRD target. ViGeneron receives an upfront payment and research funding. Regeneron has an option for an exclusive license to develop, commercialize and manufacture the vgAAV-based product for the specific target. ViGeneron is eligible to receive an option exercise fee, development and commercial milestone payments, plus royalties on net sales.

ViGenerons vgAAV vector platform is designed to overcome the limitations of existing adeno-associated virus (AAV)-based gene therapies. To date, therapeutically impactful targeting of photoreceptors relies on subretinal vector delivery, which harbors substantial risks of retinal detachment and collateral damage, often without achieving widespread photoreceptor transduction. vgAAV vectors could potentially enable the efficient transduction of target cells via intravitreal injection that allows lateral spreading and minimizes the risk of retinal detachment caused by conventional subretinal injection.

We are delighted to work with Regeneron to potentially provide an intravitreally delivered gene therapy for patients suffering from an inherited eye disease, said Dr. Caroline Man Xu, Co-founder and CEO of ViGeneron. This agreement with Regeneron further validates the potential of our vgAAV platform, which is excellent for us and also delivers a deal value that contributes financing for our platform and proprietary program development activities. Furthermore, it fits into our strategy of developing proprietary programs for selected retinal targets through clinical trials, while maximizing our technology platforms for additional collaboration programs in retinal diseases, CNS and other disease areas with bellwether biopharma. Our aim is to overcome the current limitations of gene therapy and to bring a novel therapeutic approach to patients in need, she added.

About ViGeneron

ViGeneron is dedicated to bringing gene therapy innovations to people in need. The company is advancing its proprietary gene therapy pipeline to treat ophthalmic diseases, while partnering with leading biopharmaceutical players in retinal diseases, CNS, and other disease areas. ViGenerons two novel next-generation gene therapy platforms are geared towards addressing the limitations of existing adeno-associated virus (AAV)-based gene therapies. The first, vgAAV vector platform, enables a superior transduction efficiency of target cells and is designed to overcome biological barriers, thus enabling novel, less invasive routes of administration such as intravitreal injections. The second, REVeRT (REconstitution Via mRNA Trans-splicing) technology platform, allows efficient reconstitution of large genes (>5Kb) in various tissues such as retina, brain, heart, liver, and skeletal muscle. Privately-owned ViGeneron was founded in 2017 by a seasoned team with in-depth experience in AAV vector technology and clinical ophthalmic gene therapy programs and is located in Munich, Germany. For further information, please visit http://www.vigeneron.com

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ViGeneron signs gene therapy strategic collaboration and option agreement with Regeneron for one inherited retinal disease target - BioSpace

Key MessageWhat is already known on this topic

Electrophysiological assessment of eyes with choroidal detachment, a common postoperative change of glaucoma surgery, has not been reported previously.

In the absence of choroidal detachment, rapid functional improvement was observed in the first, second and third order retinal neurons within several days of glaucoma filtration surgery.

Glaucoma, an irreversible disease, is characterised by the loss of retinal ganglion cells (RGCs) and their axons in the retina, with progressive optic-nerve damage and characteristic visual-field defects.1 2 It is the second most common cause of preventable blindness in the world.3 In 2020, 3.6million people over the age of 50 worldwide lost their vision because of glaucoma.4 Visual-field loss typically becomes detectable only after a large number of RGCs are lost.5 RGC damage can be detected by measuring retinal nerve fibre layer (RNFL) thickness using optical coherence tomography (OCT) to capture morphological changes in the early stages of glaucoma.6 The reversibility of some glaucoma-related changes, such as optic disc cupping, lamina cribrosa displacement,7 vessel density and ocular blood flow,8 following intraocular pressure (IOP) reduction in patients with glaucoma has been reported.

The photopic negative response (PhNR), an electroretinographic (ERG) component, is an objective parameter that can be used to estimate RGC function.8 9 It consists of a slow negative wave that follows the positive b-wave of the ERG and is derived from the inner retinal layers, specifically the RGC layer.8 The PhNR amplitude and PhNR/b-wave ratio, defined as PhNR divided by the b-wave, have been reported to worsen in glaucoma.8 9

Investigations of the function of RGCs810 as well as of their microstructure6 11 12 have contributed to the understanding and diagnosis of the pathophysiology of glaucoma. Interestingly, several studies have shown that the PhNR amplitude is significantly lower in glaucomatous eyes than in normal eyes.8 9 Niyadurupola et al10 and Tang et al13 reported that lowering the IOP led to electrophysiological RGC improvement. These studies reported improvements in PhNR in ocular hypertension and glaucoma after several months of IOP-lowering treatments, including eye-drops, laser therapy and surgery. However, there is no information on how early this functional RGC improvement occurs after IOP reduction following glaucoma filtration surgery. Further, there has been no electrophysiological assessment of eyes that developed choroidal detachment (CD), a common postoperative change of glaucoma surgery.14 15

In this study, we evaluated RGC function in the early postoperative period in glaucomatous eyes undergoing filtration surgery using full-field ERG and skin electrodes. Further, we compared these changes in eyes with and without CD.

Patients who underwent glaucoma filtration surgery and preoperative and postoperative ERG recordings at Saitama Medical University Hospital between September 2020 and June 2021 were included. All patients underwent a comprehensive pre-and postoperative ophthalmologic examination, including visual acuity testing, a slit-lamp biomicroscopy and IOP measurement with Goldman applanation tonometry. The most recent preoperative values were used to assess visual acuity. Visual-field tests were performed within 3 months preoperatively. Standard automated perimetry was performed with the Humphrey Field Analyzer (Carl Zeiss Meditec, Jena, Germany) using the 24-2 Swedish Interactive Thresholding Algorithm standard threshold. We measured the axial length (AL) and central corneal thickness (CCT) (Optical Biometer OA-2000, Tomey, Nagoya, Japan) within 3 months preoperatively. All participants underwent cross-sectional imaging to measure the circumpapillary RNFL thickness at each visit using spectral domain OCT (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany).

Glaucoma was diagnosed based on: (1) glaucomatous changes in the optic nerve head (ONH) observed with fundus photography, such as a vertical cup-to-disc ratio 0.7, rim notch with a rim width 0.1 and/or an RNFL defect (with its edge at the ONH margin greater than that at a major retinal vessel) diverging in an arcuate or wedge shape; (2) glaucomatous visual field defects that met at least one of the Anderson-Patella criteria, that is, a cluster of 3 points in the pattern deviation plot in a single hemifield (superior/inferior) with p<0.05, one of which must have been p<0.01; a glaucoma hemifield test result outside the normal limits, or an abnormal pattern deviation with p<0.05.16 The included patients had manifest glaucoma deemed to require glaucoma surgery owing to high IOP or evidence of progression in the visual field. All glaucoma subtypes and treatment modalities were included. Patients with visual acuity 20/200 were included in the study, whereas those with diabetic retinopathy, and insufficient ERG quality (described in detail below) were excluded. No exclusion criteria were applied for AL, refractive errors, CCT or past ocular surgery history if the patients fulfilled the inclusion criteria. The patients were divided into two groups according to the presence or absence of CD after glaucoma filtration surgery. The presence of CD and CD grading were determined using ultra-widefield fundus photography (California, Nikon, Tokyo, Japan) and grading criteria as previously reported.17

Full-field ERG was recorded using the RETeval system (LKC Technologies, Gaithersburg, MD; Welch Allyn, Skaneateles Falls, New York, USA), a portable ERG device that uses skin electrodes. The pupils were dilated with topical 0.5% tropicamide and 0.5% phenylephrine hydrochloride. The patient adapted to the background light prior to testing. Sensor strips of skin electrodes were carefully placed 2mm below the lower eyelid margin after cleaning the skin with an 80% ethanol-impregnated solution and connected to a lead wire. The stimuli consisted of a red flashing light (intensity of 1.0cd-s/m2, stimulus duration of 4 ms) on a stable blue background light (10cd/m2). Two hundred flashes were delivered at a frequency of 3.4Hz, which has been reported to achieve a good balance between testing time and signal quality.18 Signal acquisition was performed at a sampling frequency of 2kHz.

The recording time was 220ms, including 100ms of prestimulus recordings. The implicit times and amplitudes of the ERGs were automatically analysed using the software integrated into the RETeval system. The a-wave amplitude was measured from the average pre-stimulus mean baseline to the a-wave trough. The b-wave amplitude was measured from the a-wave trough to the b-wave peak; the a-wave and b-wave peak times were measured from the time of the flash to the peak of the wave.19 The PhNR was selected as the most negative trough appearing behind the b-wave according to the standard of the International Society for Clinical Electrophysiology of Vision.8 Its amplitude can be measured in various ways; in this study, it was measured from the b-wave peak to the PhNR trough (PT) (as shown in online supplemental figure 1). We also analysed the PT/b-wave amplitude ratio; the PT amplitude and PT/b-wave amplitude ratio have been reported to be highly reproducible.20 These indices were analysed using the well-recorded ERG waves that had a stable recorded baseline. When the last point of the recorded waveform deviated from the baseline level before recording by 3SD or more of the noise amplitude, it was judged that the baseline of the recorded waveform was unstable and defined as an ERG wave with insufficient quality. The fluctuation range of the baseline before recording was regarded as the noise amplitude. It was measured in 10 randomly selected eyes according to the manufacturers instructions and was measured to be 1.30.9 V. Therefore, the reference value was defined as 5.1 V. Preoperative ERGs were recorded the day before surgery, and postoperative ERGs were measured within 2 weeks.

The significance of the differences within the groups was compared using the paired t-test and that between the groups was compared using Students t-test. Pearson 2 and Fishers exact test were used for categorical variables. We analysed the relationship between the change in PhNR amplitude and various structural and functional factors such as age, AL, CCT, preoperative and postoperative IOP, preoperative mean deviation (MD) values by HFA 24-2, past surgical history, presence or absence of postoperative CD, change in visual acuity and self-reported systemic diseases. Decimal visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Variables with p<0.10 in the univariate analysis were used for multivariate analysis. In addition, to confirm the intersession reproducibility, we randomly selected 15 patients and measured the preoperative and postoperative PhNR amplitudes and implicit times in the non-operated eye and calculated the coefficient of variation (CV) values. Statistical significance was set at p<0.05 based on a threshold two tailed. Distributed variables are reported as mean (95%CI), except for age, which is reported as the median (quartile). We used the JMP Pro V.16 software (SAS Institute) for the analyses.

Figure 1 shows a flow diagram of the study patients. Seventy-four patients were initially enrolled in the study. Seventeen patients were excluded because of poor visual acuity (five eyes), diabetic retinopathy (five eyes) and insufficient ERG quality (seven eyes; three eyes had insufficient quality preoperatively, two eyes had insufficient quality postoperatively and two eyes met the criteria for insufficient quality in both preoperative and postoperative measurements). Among the 4 eyes that showed insufficient ERG quality and IOP of less than 10mm Hg, 2 eyes showed CD (2 eyes out of 11 eyes: 18.2%), and the other 2 eyes had no CD (2 eyes out of 46 eyes: 4.3%), and there was no significant difference. Thus, the data of 57 patients were included in the analysis, including those of 46 patients without CD and 11 with CD. Table 1 summarises the characteristics of the two groups. There were no significant between-group differences in age, gender distribution, preoperative best-corrected visual acuity, preoperative mean deviation, preoperative IOP, distribution of glaucoma subtypes and whether cataract surgery was concomitantly performed. As expected, the postoperative IOP value was significantly lower in the CD group (6.4 (4.6 to 8.1)mm Hg, mean (95%CI)) than in the non-CD group (9.7 (8.6 to 10.7)) mm Hg (p=0.003). Other factors such as age, gender distribution, preoperative IOP, preoperative MD value, CCT, AL, self-reported systemic diseases and past ocular surgery history were not significantly different between the groups.

Patientcharacteristics

Flow diagram of study patients. CD, choroidal detachment; ERG, electroretinography.

Figure 2 shows three eyes of the representative cases from the non-CD group. Compared with before glaucoma surgery, IOP decreased and PhNR amplitude improved after surgery in all three cases. Figure 3 shows two eyes of representative cases from the CD group. In both cases, transient CD (grade 2) occurred after glaucoma surgery, and PhNR amplitude deteriorated compared with before surgery. CD recovered spontaneously and disappeared after 1month and the PhNR amplitude also improved.

Representative cases from the non-CD group of preoperative (left column) and postoperative (middle column) electroretinography results and widefield fundus photography (right column). Case 1 was an 84-year-old man. His IOP was 23mm Hg preoperatively. The day after the surgery, his IOP decreased to 11mm Hg and his PhNR amplitude improved. Case 2 was a 64-year-old man. His IOP was 28 mm Hg preoperatively, and on the seventh day of surgery, his IOP decreased to 7mm Hg and his PhNR amplitude improved slightly. Case 3 was a 72-year-old man. His IOP was 20mm Hg preoperatively, and on the third day of surgery, his IOP decreased to 9mm Hg and his PhNR amplitude improved slightly. CD, choroidal detachment; IOP, intraocular pressure; PhNR, photopic negative response.

Representative cases of the CD group preoperatively (left column), early postoperatively with CD (middle column), and postoperatively after spontaneous recovery of CD (right column). Case 4 was a 74-year-old woman. Six days after surgery, the IOP decreased to 7mm Hg, and a grade 2 CD was confirmed by wide-angle fundus photography. PhNR amplitude had also worsened. One month later, the CD recovered spontaneously and the PhNR amplitude improved. Case 5 was a 73-year-old woman. The preoperative IOP was 28mm Hg. On postoperative day 4, the IOP was 10mm Hg, but wide-angle fundus photography showed grade 2 CD, and the amplitude of the PhNR also deteriorated. One month later, the CD recovered spontaneously and the amplitude of the PhNR improved. CD, choroidal detachment; IOP, intraocular pressure; PhNR, photopic negative response.

The changes in ERG parameters preoperatively and postoperatively for each group are summarised in table 2. The scatter plots in figure 4 show the changes in the PhNR implicit time and amplitude and the PhNR/b-wave amplitude ratio.

Scatter plots showing the change in PhNR implicit time and amplitude and the PhNR/b-wave amplitude ratio. Scatter plots of each PhNR parameter pre -and postoperatively. The x-axis shows the preoperative values, and the y-axis shows the postoperative values. In the plot, the circle indicates the non-CD group and the cross indicates the CD group. (A) PhNR amplitude. (B) PhNR/b-wave amplitude ratio. (C) PhNR implicit time. CD, choroidal detachment; PhNR, photopic negative response.

Comparison of full-field ERG parameters before and after the operation

In the non-CD group, the PhNR amplitude, PhNR/b-wave amplitude ratio and PhNR implicit time significantly improved after surgery. The PhNR amplitude changed from mean (95%CI) 17.3 (15.6 to 19.1) V to 18.7 (16.7 to 20.6) V (p=0.008). The PhNR/b-wave amplitude ratio changed from 0.86 (0.84 to 0.89) to 0.90 (0.87 to 0.93; p=0.002). The PhNR implicit time changed from 75.3 (72.6 to 78.0) to 72.3 (70.4 to 74.3) ms (p=0.039). In addition, the a-wave and b-wave implicit times significantly improved after surgery. The a-wave implicit time changed from 14.8 (14.4 to 15.2) ms to 14.3 (14.0 to 14.7) ms (p=0.027). The b-wave implicit time changed from 32.2 (31.5 to 32.9) ms to 31.4 (30.9 to 32.0) ms (p=0.004).

In the CD group, the PhNR amplitude significantly deteriorated after surgery. The PhNR amplitude changed from 17.0 (12.4 to 21.5) V to 11.4 (7.7 to 15.0) V (p=0.002). In addition, the a-wave and b-wave amplitudes significantly deteriorated after surgery. The a-wave amplitude time changed from 4.9 (6.0 to 3.8) V to 3.1 (4.2 to 2.0) V (p=0.001). The b-wave amplitude changed from 19.1 (14.5 to 23.8) V to 13.3 (9.3 to 17.3) V (p=0.001). The PhNR/b-wave amplitude ratio, PhNR implicit time, a-wave amplitude, and b-wave amplitude did not change significantly.

Figure 5 shows the distribution of change in the PhNR amplitude in the CD group and the non-CD group. The postoperative change in PhNR amplitude was significantly lower in the CD group than in the non-CD group (p<0.001). Table 3 shows the results from the univariate and multivariate models investigating the relationship between the change in the PhNR amplitude and related factors. Postoperative IOP (p=0.031) and postoperative CD (p<0.001) were significantly associated with change in the PhNR amplitude in the univariate models. We separately examined the presence of postoperative CD and postoperative CD gradings with two different multivariable models. In the multivariate analysis, the presence of postoperative CD, CD grading 1 (p=0.048) and 3 (p=0.004) were significantly correlated with change in the PhNR amplitude.

Association between change in PhNR amplitude and ocular variables: univariate and multivariable analysis

Distribution of change in the PhNR amplitude in the CD group and the non-CD group. CD, choroidal detachment; PhNR, photopic negative response.

The CV values were 12.4% (95% CI 7.5% to 17.4%) for the PhNR amplitude, 2.4% (95% CI 1.1% to 3.7%) for PhNR/b-wave amplitude ratio and 6.0% (95% CI2.6% to 9.5%) for PhNR implicit time.

In this study, we demonstrated the rapid improvement in RGC function within several days after glaucoma filtration surgery by measuring PhNR using skin electrodes in the same eye preoperatively and postoperatively. The PhNR amplitude worsened after glaucoma surgery in patients with CD because of overfiltration.

Interestingly, the a-wave, b-wave and PhNR improved after glaucoma filtration surgery. This suggests the possibility that the reduction in IOP may be related to changes in blood flow in deeper layers. Deep macular microvasculature alteration in glaucomatous eyes has recently been reported.11 21 Further studies on whether this deep circulatory impairment can be improved by lowering IOP would provide an answer. Using OCTA, we recently reported microcirculatory disturbances in the macula before and after glaucoma surgery.22 23 The foveal avascular zone area was significantly reduced at 3 months after surgery. We concluded that capillary circulation may improve to a level detectable with OCTA. IOP, microcirculation and physiological improvements in function are considered closely related and act together quite early in the postoperative period.

RETeval is a relatively new ERG recording system that uses skin electrodes and is less invasive.24 RETeval PhNR is simple, reproducible and carries a low risk of infection when observing acute functional changes in the dense perioperative period.24 25 Using this method, it was possible to observe retinal function 2hours after vitreous injection26 and several days after vitrectomy.27 In this study, we showed that skin electrode ERG can be used to evaluate retinal function in the early postoperative period, even in eyes after filtration surgery that cannot tolerate contact lenses and DTL electrodes.

Another notable finding of this study is the significant association between the presence of CD soon after postoperative glaucoma filtration surgery and changes in retinal function observed using skin electrode ERG. In some situations, mild CD is difficult to detect. Objective diagnosis of the presence or absence of CD in the early postoperative period is practical and could help decide on further management.28 This study showed that the behaviour of the ERG components recorded in the early postoperative period strongly correlated with the presence of CD. The a-wave, b-wave and PhNR waves deteriorated in the CD group. First, choroidal function may play a role. Miyake et al15 analysed the electrooculogram of eyes with rhegmatogenous retinal detachment (RRD) and found that the preoperative values were significantly lower in eyes with CD than in those without. Choroidal dysfunction may affect outer retinal layer function, leading to changes in the a-wave and subsequently in the b-wave and PhNR. Second, another explanation is that the inner protrusion of the retinal surface caused by CD may have reduced the response of the ERG because of unequal stimulus light exposure. The fact that the amplitude deteriorated but the implicit time was relatively maintained is consistent with the latter explanation. Third, the effect of IOP on ERG changes should be considered. Miyake et al29 used ERG to monitor retinal function during scleral buckling surgery in eyes with RRD. They observed a marked decrease in retinal function immediately after subretinal fluid drainage, but it improved with increased IOP caused by buckling. Therefore, the authors stated that the functional reduction was attributed to the effect of low IOP. In this study, eyes with CD also had a lower IOP than those without. However, rapid IOP reduction does not always cause reduction in the ERG response, as shown by studies of electrophysiological monitoring during intravitreal injection.30 31 Further studies are required to validate this mechanism.

Recently, Shin et al reported on CD grading using wide-angle photographs.17 The widespread use of wide-angle fundus photography has enabled objective interpretation of the degree of CD. In this study, we showed a significant association between CD grading and PhNR amplitude change. They showed the risk of CD was associated with pseudoexfoliation glaucoma, older age, and previous cataract surgery. Though there was no statistically significant difference between the two groups in this study, the results were consistent with the past reports by Shin as the CD group was older, had more cases of pseudoexfoliation glaucoma, systemic hypertension and diabetes, and previous cataract surgery.

The limitations of this study include its retrospective design, small sample size and lack of long-term postoperative data. It is possible that the deterioration of the PhNR amplitude may improve with the improvement of CD, and it is unclear how long the improvement of the PhNR amplitude will persist. Further studies with longer follow-up periods will clarify these associations. Second, it can be argued that the improved PhNR after surgery could be a result of improved media factors rather than the recovery of retinal function. Preoperative corneal oedema and combined cataract surgery may influence ERG quantitative measurements. In this study, the proportion of patients with a history past ocular surgery history was similar in the groups. Simultaneous cataract surgery was performed in 22 out of 46 eyes (47.8%) in the CD group and 3 out of 11 eyes (27.2%) in the non-CD group, and cataract surgery may have affected the postoperative changes in ERG. Tanikawa et al32 conducted a detailed study on the effects of cataract surgery on ERG. They reported a significant increase in the a- and b-wave amplitudes, but not in PhNR, after cataract surgery. In addition, after excluding eyes with preoperative IOP higher than 30mm Hg (five eyes) from the analysis, the results were similar (online supplemental table 1). Thus, the impact of media factors on PhNR, if any, may be considered inconsequential for the results of this study. Third, the influence of the hypotonic state on the ERG quality may be a cause of concern for selection bias. The comparisons of the ERG parameters between CD and non-CD groups should be interpreted with caution; however, the incidence of the excluded eyes due to insufficient ERG similar in the groups (data not shown).

In conclusion, even in the early postoperative period within several days, the PhNR amplitude increased with IOP lowering following filtration surgery, and showed rapid functional recovery. However, the appearance of CD identified by wide-field fundus photography suggests that CD may arrest functional recovery, at least temporarily. The present results enhance understanding of the structural and functional recovery after glaucoma surgery and the role of postoperative CD.

Data are available on reasonable request. The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

Consent obtained directly from patient(s)

The present study was part of a prospective longitudinal study approved by the Ethics Committee of the Saitama Medical University (No. 15138) and conducted in accordance with the tenets of the Declaration of Helsinki. The detailed design of this longitudinal study has been described previously. The Ethics Committee of Saitama Medical University approved the present study and waived the requirement of additional informed consent due to the retrospective nature of the study (No. byou2021-074).

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Early changes in photopic negative response in eyes with glaucoma with and without choroidal detachment after filtration surgery - British Journal of...

Newswise The road from discovering a potential drug to getting the therapy into the hands of patients is a long and uncertain one.

Konstantin Petrukhin, Ph.D., ought to know.

In 2011, after years working at the bench, the professor of ophthalmic sciences at Columbia University Medical Center, discovered a promising drug candidate for treating the most common form of age-related macular degeneration (AMD). This blinding eye disease affects millions of Americans, and atrophic or dry AMD accounts for 90% of cases. There is currently no treatment for dry AMD.

The therapy, known as LBS-008 (formerly BPN-14967), appears to be promising for other retinal degenerative diseases such as Stargardt disease, a rare, inherited condition that causes vision loss during childhood and young adulthood.

The cherry on top: Petrukhin identified a biomarker that could easily be measured in a persons blood to confirm the drugs level of activity and fine tune dosage. LBS-008 is a tablet taken by mouth, sparing patients the need for an injection into the eye, which is a common mode of delivery for therapies that must reach the light-sensitive retinal tissue at the back of the eye.

Despite all that LBS-008 had in its favor, Petrukhin had only cleared the first hurdle. The next would involve finding a biopharmaceutical firm willing to take the risk of shepherding the new drug to the market.

For every drug that successfully makes it into the hands of patients, nine fail somewhere along the clinical trial pipeline.[1] On average, it can take up to 15 years and $1 billion to bring a new drug to market, accounting for the failed drug candidates.[2]

Much of that time and money is spent meeting rigorous regulatory requirements established by the U.S. Food and Drug Administration. These requirements are in place to safeguard the health of patients. Before a new drug is FDA-approved, it must demonstrate safety and efficacy in a lengthy three-phase clinical trial process.

And before clinical trials can even begin testing in humans, the FDA requires preliminary support for the safety, efficacy, and quality of the investigational therapy. That means information about the agents performance in preclinical animal studies assessing efficacy and toxicology, detailed clinical protocols and manufacturing plans.

It takes a team of experts with a wide range of expertise to advance a candidate drug to clinical trials, Petrukhin said. Basic science researchers in academia typically do not have access to all the necessary skills to get their novel therapeutics strategies to the point where a biopharmaceutical firm would be interested in taking on a promising drug through the clinical trials process.

For that expertise, Petrukhin turned to the National Institutes of Health Blueprint Neurotherapeutics Network for Small Molecules. Launched in 2011, the network provides a framework for researchers like Petrukhin, who have a promising candidate treatment for an unmet medical need, to attract pharmaceutical company interest.

How the NIH Blueprint program works

The network, which is funded and administered by a consortium of NIH institutes, including the National Eye Institute, provides principal investigators like Petrukhin access to a full range of industry-style drug development services and expertise. Each project forms a lead development team composed of the principal investigator, as well as NIH staff and industry consultants hired by NIH. The network provides principal investigators with access to Contract Research Organizations (CROs) and a team providing cross-functional expertise from assay development and pharmacology to medicinal chemistry, pharmacokinetics, toxicology, formulation development, and Phase I clinical testing.

If a researchers project requires a consultant that has a specific type of expertise such as regulatory affairs or drug manufacturing, we have a diverse group of consultants with years of experience in the pharmaceutical industry who provide guidance in areas such as the FDA regulatory process and the steps involved in developing a useful drug product, free of charge. Essentially, researchers have access to a virtual pharma company tailored to their project through their lead development team and NIH contracts, said Mary Ann Pelleymounter, Ph.D., a scientific project manager for the Blueprint Neurotherapeutics Network for Small Molecules.

Academic and small business researchers are provided with the tools and resources to navigate the drug discovery process in an efficient way that is intended to optimize the probability of success, added Pelleymounter who managed Petrukhins lead development team.

The Blueprint Neurotherapeutics Network was NIHs response to the fact that most nervous system and neurodegenerative disorders lack effective treatment, and most of the potential neurotherapeutic agents identified from basic research do not make it to human testing.

As tough as it is to bring new drugs to market in general, neurotherapeutics have an even steeper hill to climb. They have a long track record of failure and a limited pool of validated treatment targets and strategies on which to build, which resulted in pharma companies exiting the neuroscience research area, said Charles Cywin, Ph.D., program director for the Blueprint Neurotherapeutics Network.

Inherited neurological disorders also tend to affect relatively small populations, which reduces the potential upside for a company taking on the risk.

Finally, neurotherapeutic clinical trials often are expensive because many of the disorders, such as AMD, are neurodegenerative, progressing over years, necessitating lengthy and costly trials to determine if a treatment is working.

The Blueprint Network aims to de-risk candidate therapeutic agents to the point that these projects are attractive investments for pharma, biotech and venture firms, and allows these exciting basic research findings to become potential new drugs to reach patients efficiently, Pelleymounter said.

In 2011, Petrukhins project was selected by the NIH Blueprint Program and received sufficient funding and contract resources to support development of LBS-008 from early discovery through Phase Ia clinical testing.

In 2017, the San Diego-based biopharmaceutical company Belite Bio Inc. (formerly Lin Bioscience) selected LBS-008 for its portfolio to support clinical testing of this candidate therapeutic. By June 2021, the company had launched a late-stage Phase 3 clinical trial of LBS-008 in patients with Stargardt disease. As a potential treatment for a rare disease, testing the drug first in Stargardt enabled LBS-008 to be granted an orphan-drug designation, which qualifies Belite Bio for tax credits and an extended period of market exclusivity after approval. If LBS-008 is approved, it will accelerate the clinical trial process for an atrophic AMD indication.

Under the agreement, Belite Bio holds exclusive global licensing rights. Along with other co-inventors, Petrukhin maintains relevant patents. Columbia University holds the rights to the intellectual property portfolio. If approved, the drug will be marketed as Tinlarebant.

How the LBS-008 therapy works

Petrukhin designed his therapeutic strategy based on a long-observed phenomenon in patients with atrophic AMD and Stargardt disease. Their retinas tend to have an accumulation of lipofuscin, a yellow-brown lipid-based substance associated with aging. Granules of lipofuscin accumulate in a retinal layer called the retinal pigment epithelium (RPE), which supports the health of light-sensing photoreceptors. In both atrophic AMD and Stargardt disease, vision loss occurs when photoreceptors die, but their death happens secondary to the loss of RPE cells. Petrukhin and others hypothesized that reducing harm from lipofuscin might prolong RPE and photoreceptor survival.

The best studied toxic component of lipofuscin is the bisretinoid A2E, a by-product of the normal visual cycle, the vital biochemical pathway that regenerates visual pigment, and is important for converting light (photons) into electrical signals sent from the retina to the brain.

A2E production depends on the influx of retinol from blood to the RPE. Whats more, retinol uptake from blood circulation is dependent on the function of retinol-binding protein 4 (RBP4).

Petrukhin asked whether reducing the retinoid load of the visual cycle with an RBP4 antagonist might reduce A2E production just enough to stave off AMD and Stargardt disease, without interfering too much with the necessary biochemical pathway required for vision.

In his search for a way to inhibit RBP4, Petrukhin came across some papers describing an RBP4 antagonist compound that had initially been developed by the pharmaceutical company Amgen as a potential treatment for diabetes. Long since shelved for diabetes, Petrukhin began tests to see if the RBP4 antagonist might lead to a therapeutic reduction of lipofuscin bisretinoids. That compound (called A1120) was a starting point for optimization that eventually yielded LBS-008, a drug candidate that is currently in clinical development.

In unpublished mouse studies, LBS-008 reduced levels of RBP4 in the blood by 93% after 12 weeks, and A2E levels were reduced by 80% in treated mice compared to controls.

Furthermore, in mouse models of Stargardt disease, compared with controls, LBS-008-treated animals had significantly greater preservation in the thickness of their outer nuclear layer, a cell layer that consists of photoreceptors that becomes thinner with disease-related damage.

Petrukhin notes that several other companies have since adopted similar RBP4 antagonist strategies for reducing lipofuscin bisretinoids. So, the field has become very crowded, which tells we made the right choice, he said.

Today, Petrukhins lab is continuing to explore optimal strategies for developing the next generation of RBP4 antagonists, which are not only potential therapies for eye diseases, but may also be used as a treatment for metabolic diseases such as non-alcoholic fatty liver disease and type 2 diabetes.

Building on the success of the initial Blueprint Neurotherapeutics Network for Small Molecules (that is, therapies like Petrukhins that enter cells and work at a molecular level), the program recently expanded to support lead optimization for biologic therapies, which are treatments derived from substances made from living organisms.

This is an exciting new opportunity for vision scientists working on some of the most promising biologic-based therapies, such as gene therapies, or cell-replacement therapies, said Thomas Greenwell, Ph.D., a program director for the NEI and for Blueprint. To learn more about the Blueprint Neurotherapeutics Network: Biologic-based Drug Discovery and Development for Disorders of the Nervous System, visit https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics

Clinical trials testing LBS-008, also known as BPN-14967 are NCT05244304, NCT04005807, NCT05266014, NCT03735810.

Links

Blueprint Neurotherapeutics Network (BPN) for Small Molecules

Age-related macular degeneration

Stargardt disease

Safety and Tolerability Study ofLBS-008in Healthy Adult Subjects After Single and Multiple Doses on Clinical Trials.gov

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Advancing a Treatment for a Common Eye Disease That Lacks One - Newswise