Seeking to address a rising tide of retinal disease, Boehringer Ingelheim GmbH has agreed to pay Newton, Mass.-based Inflammasome Therapeutics Inc. as much as $160 million for rights to use its intravitreal drug delivery technology with up to three Boehringer compounds.

About 82 million people in seven key pharma markets have been affected by one of the three major forms of retinal disease, age-related macular degeneration (AMD), diabetic retinopathy and diabetic macular edema, Boehringer said. Aging populations and the global diabetes epidemic are poised to drive that number higher in the decade to come. Reducing patient burdens, such as repeated trips for specialty care, could potentially play a significant role in successful treatment.

The exact mechanisms of delivery under development haven't been fully disclosed yet, though a biodegradable gel formulation is one potential avenue. Inflammasome has developed new IP covering the administration of compounds it's developing as sustained-release depot formulations, too.

Boehringer has three disclosed assets for retinopathies in active development, according to Cortellis, including two phase I candidates for the potential intravitreal treatment of AMD. Another, a possible oral treatment for nonalcoholic steatohepatitis and diabetic retinopathy, was bought from Sydney-based Pharmaxis Ltd. and is in phase II. (See BioWorld, Aug. 25, 2017, and Aug. 16, 2018.)

Inflammasome is entitled to receive up to $160 million in up front, research and development support and milestone-based development payments as well as tiered royalties based on potential future commercial sales of developed products and other events.

No strangers to the eye

Founded in late 2016 by former Psivida Corp. CEO Paul Ashton and degenerative disease expert Jayakrishna Ambati, Inflammasome Therapeutics has been financed to date by Seoul-based specialty pharma Taejoon Pharm Co. Ltd. Each has added unique expertise to the company's efforts, which are expected to move two initial candidates – one for an ocular indication and another for a systemic disease – into the clinic next year, Ashton told BioWorld.

During his time at Psivida (now Eyepoint Pharmaceuticals Inc.) and Controlled Delivery Systems, Ashton led the team that developed multiple sustained-release FDA-approved back-of-the-eye drugs, including Vitrasert (ganciclovir), Retisert (fluocinolone) and the fluocinolone acetonide implants Iluvien and Yutiq, for diabetic macular edema and chronic noninfectious uveitis, respectively.

Taejoon Pharm, too, has been long active in the ophthalmic space, producing a wide range of agents since its founding in 1987, including contrast media, latanoprost and polyethylene glycol. The company is now seeking to expand its global footprint, positioning its CEO, Joon-youb Lee, in a key role as a member of Inflammasome's board.

Ambati, meanwhile, brings deep scientific expertise in degenerative diseases to the table, including insights developed in his University of Virginia lab. He first reported in 2014 that nucleoside reverse transcriptase inhibitors (NRTIs) possess intrinsic anti-inflammatory activity. However, while proving highly effective in multiple, disease-relevant preclinical models of inflammasome-mediated diseases, such as macular degeneration and type 2 diabetes, he also found that mitochondrial toxicity and other side effects precluded their use in those contexts.

In seeking to overcome that challenge, Ambati and his colleague have found that blocking phosphorylation of NRTIs can create a new type of molecule which they have called kamuvudines. Kamuvudines, the stars of Inflammasome Therapeutics' pipeline, have no antiviral activity, no measurable toxicity to date, and are at least as effective as NRTIs against inflammasomes. "We now have a new class of drugs that are potentially going to be very useful against a huge number of inflammatory-mediated diseases," Ashton said.

Aberrant actors and storied drugs

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain dysregulated inflammatory responses. In Alzheimer's disease (AD), multiple sclerosis (MS), macular degeneration and type 2 diabetes, though, they stay active for too long, causing chronic release of inflammatory molecules such as caspase-1, IL-18 and IL-1 beta. That, in turn, can cause progressive tissue damage and disease progression.

Inflammasome Therapeutics was founded to develop therapies that, through sustained delivery, combat that aberrant response, for instance stopping the progression of geographic atrophy, the most severe form of dry AMD for which no therapy is currently approved. The company also sees opportunities in addressing the ongoing low-grade inflammation that is closely involved with the pathogenesis of type 2 diabetes and associated complications and the pathologic role of inflammasome activation in MS and AD.

In addition to pursuing an increasingly hot target, the company is likely to gain attention for the involvement of award-winning scientist Napoleone Ferrara, whose work led to the development of Avastin (bevacizumab) and Lucentis (ranibizumab). Ferrara, now a professor of pathology of opthalmology at the University of California, San Diego is a member of the company's board.

About 82 million people in seven key pharma markets have been affected by one of the three major forms of retinal disease, age-related macular degeneration (AMD), diabetic retinopathy and diabetic macular edema, Boehringer said. Aging populations and the global diabetes epidemic are poised to drive that number higher in the decade to come. Reducing patient burdens, such as repeated trips for specialty care, could potentially play a significant role in successful treatment.

The exact mechanisms of delivery under development haven't been fully disclosed yet, though a biodegradable gel formulation is one potential avenue. Inflammasome has developed new IP covering the administration of compounds it's developing as sustained-release depot formulations, too.

Boehringer has three disclosed assets for retinopathies in active development, according to Cortellis, including two phase I candidates for the potential intravitreal treatment of AMD. Another, a possible oral treatment for nonalcoholic steatohepatitis and diabetic retinopathy, was bought from Sydney-based Pharmaxis Ltd. and is in phase II. (See BioWorld, Aug. 25, 2017, and Aug. 16, 2018.)

Inflammasome is entitled to receive up to $160 million in up front, research and development support and milestone-based development payments as well as tiered royalties based on potential future commercial sales of developed products and other events.

No strangers to the eye

Founded in late 2016 by former Psivida Corp. CEO Paul Ashton and degenerative disease expert Jayakrishna Ambati, Inflammasome Therapeutics has been financed to date by Seoul-based specialty pharma Taejoon Pharm Co. Ltd. Each has added unique expertise to the company's efforts, which are expected to move two initial candidates – one for an ocular indication and another for a systemic disease – into the clinic next year, Ashton told BioWorld.

During his time at Psivida (now Eyepoint Pharmaceuticals Inc.) and Controlled Delivery Systems, Ashton led the team that developed multiple sustained-release FDA-approved back-of-the-eye drugs, including Vitrasert (ganciclovir), Retisert (fluocinolone) and the fluocinolone acetonide implants Iluvien and Yutiq, for diabetic macular edema and chronic noninfectious uveitis, respectively.

Taejoon Pharm, too, has been long active in the ophthalmic space, producing a wide range of agents since its founding in 1987, including contrast media, latanoprost and polyethylene glycol. The company is now seeking to expand its global footprint, positioning its CEO, Joon-youb Lee, in a key role as a member of Inflammasome's board.

Ambati, meanwhile, brings deep scientific expertise in degenerative diseases to the table, including insights developed in his University of Virginia lab. He first reported in 2014 that nucleoside reverse transcriptase inhibitors (NRTIs) possess intrinsic anti-inflammatory activity. However, while proving highly effective in multiple, disease-relevant preclinical models of inflammasome-mediated diseases, such as macular degeneration and type 2 diabetes, he also found that mitochondrial toxicity and other side effects precluded their use in those contexts.

In seeking to overcome that challenge, Ambati and his colleague have found that blocking phosphorylation of NRTIs can create a new type of molecule which they have called kamuvudines. Kamuvudines, the stars of Inflammasome Therapeutics' pipeline, have no antiviral activity, no measurable toxicity to date, and are at least as effective as NRTIs against inflammasomes. "We now have a new class of drugs that are potentially going to be very useful against a huge number of inflammatory-mediated diseases," Ashton said.

Aberrant actors and storied drugs

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain dysregulated inflammatory responses. In Alzheimer's disease (AD), multiple sclerosis (MS), macular degeneration and type 2 diabetes, though, they stay active for too long, causing chronic release of inflammatory molecules such as caspase-1, IL-18 and IL-1 beta. That, in turn, can cause progressive tissue damage and disease progression.

Inflammasome Therapeutics was founded to develop therapies that, through sustained delivery, combat that aberrant response, for instance stopping the progression of geographic atrophy, the most severe form of dry AMD for which no therapy is currently approved. The company also sees opportunities in addressing the ongoing low-grade inflammation that is closely involved with the pathogenesis of type 2 diabetes and associated complications and the pathologic role of inflammasome activation in MS and AD.

In addition to pursuing an increasingly hot target, the company is likely to gain attention for the involvement of award-winning scientist Napoleone Ferrara, whose work led to the development of Avastin (bevacizumab) and Lucentis (ranibizumab). Ferrara, now a professor of pathology of opthalmology at the University of California, San Diego is a member of the company's board.

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