Regulus Moving Closer To Potential $25 Million Milestone Payment For Novel Kidney Disease Treatment Licensed To Sanofi

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Up to 60,000 people in the US with a rare genetic kidney disease called Alport syndrome may be in for some life-altering news in the year ahead.

Last month, Regulus Therapeutics RGLS announced completion of enrollment in the Phase 2 HERA study of lademirsen, a drug candidate for the treatment of Alport syndrome licensed exclusively to Sanofi SNY. Under the terms of the agreement, Sanofi is responsible for all remaining development and commercialization costs and Regulus is eligible for $25 million in remaining milestone payments. The degenerative kidney disease is estimated to afflict 30,000 to 60,000 patients in the US alone.

In 2020 Regulus achieved $10 million in milestone payments from Sanofi associated with the completion of transfer and verification of certain materials as well as an interim enrollment milestone for progress with the HERA study. Regulus recently announced completion of targeted enrollment and is expected to report topline results in the first half of next year. Under the terms of the Collaboration and License Agreement, Regulus is eligible to receive a $25 million milestone upon successful completion of the ongoing HERA study, or the initiation of the next phase of clinical development by Sanofi. 

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The Alport candidate was Regulus’s first clinical-stage drug discovery in kidney therapeutics. Since then, it has developed RGLS8429 for Autosomal Dominant Polycystic Kidney Disease, or ADPKD. About 160,000 people in the US are diagnosed with ADPKD, making it one of the most common genetic kidney ailments.         

The disease causes cysts in the kidneys, ultimately leading to end-stage renal disease.

The only approved drug for the condition comes from Otsuka Pharmaceuticals at a cost of approximately $200,000 a year. Its sales are approaching $1 billion a year, despite a Black Box warning due to the potential for fatal liver injury or failure requiring transplant.

Regulus is on track to submit an IND application and upon IND clearance, start a Phase 1 clinical trial of its ADPKD drug candidate in the second quarter of this year.

The drug candidates for Alport syndrome and ADPKD share common roots, both benefiting from Regulus’s core competency in microRNA biology, and Regulus is leveraging this expertise with early programs in other kidney diseases and CNS disorders where microRNAs are implicated in the disease.

Last November, Regulus completed a $34.6 million private offering of common stock at market with no warrants. The financing was led by the Federated Hermes Kaufmann Funds and New Enterprise Associates (NEA), with participation from other new and existing investors. At December 31, 2021, Regulus reported $60.4 million of cash and cash equivalents, which is projected to carry it through 2023.

The Race To Treat Alport Syndrome

The competitive landscape for potential Alport syndrome treatments made the news recently with the high-profile setback for bardoxolone, a once-promising drug being developed by Reata Pharmaceuticals RETA. On February 26 Reata said it received a Complete Response Letter (CRL) from the FDA requesting new data to support the safety and efficacy of bardoxolone in treating Alport syndrome.

There is currently no FDA-approved treatment for the disease. The CRL received by Reata, and the delays it suggests for additional studies, may move lademirsen up the leaderboard for consideration as the first-to-market drug for this rare but life-threatening disease.

Here’s a closer look at what lademirsen is meant to treat and how it works.

Alport syndrome is a genetic kidney disease featuring symptoms like hearing loss, eye abnormalities, and progressive loss of kidney function. Symptoms typically start to appear in childhood and require transplant or dialysis by early adulthood.

With no approved treatment on the market, patients are limited to medications that treat the symptoms of kidney disease. These drugs can slow the progression of Alport syndrome, but without a more long-term solution, many patients with the disease will ultimately need a kidney transplant. Even then, transplants will not restore hearing or eyesight. 

The disease causes these wide-ranging symptoms because of mutations in a person’s type IV collagen genes. Type IV collagen is key to building strong membranes that can effectively filter out toxins in the body. That same collagen is an important part of the inner ear and the lens and retina of the eye, which is why the syndrome affects all these areas.

In the kidney, poor filtration over time leads to scarring that ultimately leads to kidney failure. 

If left untreated, about 50% of men with the most common variant of Alport syndrome will develop kidney failure by the age of 25. By age 60, nearly all these men will have developed kidney failure. While the disease progression is slower for women, they may still suffer from declining kidney function, hearing loss, and eyesight problems throughout their life. 

What Is Lademirsen?

Recent research has found that microRNA-21 (miR-21) may be a culprit in Alport syndrome. The small, noncoding RNA promotes cell growth and proliferation but, when overactive or when there is too much miR-21 in the body, as there seems to be in Alport syndrome, it can cause tissue scarring, known as renal fibrosis, associated with worsening kidney function.

Lademirsen is a chemically-modified oligonucleotide (a short RNA molecule) that can bind to and stop miR-21 from functioning. In preclinical studies, lademirsen successfully slowed down renal fibrosis and increased the lifespan of the treated mice by up to 50%. 

A Phase 1 clinical trial completed in 2019 showed that the compound was well-tolerated in  patients with the disease and had promising trends in key disease markers, paving the way for Phase 2 trials. 

The drug candidate has received orphan designation in both Europe and the United States, which not only provides tax credits and other incentives to develop the drug but also grants up to seven years of US market exclusivity if it’s approved by the Food and Drug Administration (FDA).

When Is the $25 Million Payment Due?

 Sanofi has completed enrollment of the Phase 2 HERA study which will treat patients between 18 and 55 years old with weekly injections of lademirsen for 48 weeks to gather additional data on the drug’s ability to slow disease progression in patients with Alport syndrome.

Regulus could see its $25 million milestone payment in 1H 2023 if the trial posts successful results, or if lademirsen moves on to the next phase of clinical development.

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This post contains sponsored advertising content. This content is for informational purposes only and is not intended to be investing advice.

Important note, please read: Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the Company’s RGLS8429 program, including the expected timing for submitting an IND and initiating Phase 1 clinical studies, the expected timing for reporting topline data, and statements concerning the timing and future occurrence of clinical activities related to lademirsen and receipt of clinical data or associated milestones.  Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus’ current expectations and involve assumptions that may never materialize or may prove to be incorrect.  Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and in the endeavor of building a business around such drugs, and the risk additional toxicology data may be negative. In addition, while Regulus expects the COVID-19 pandemic to adversely affect its business operations and financial results, the extent of the impact on Regulus’ ability to achieve its preclinical and clinical development objectives and the value of and market for its common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat the disease.  These and other risks are described in additional detail in Regulus’ filings with the Securities and Exchange Commission, including under the “Risk Factors” heading of Regulus most recently quarterly report on Form 10-Q.  All forward-looking statements contained in this document speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This is not a solicitation of any offer to buy or sell. Redington, Inc. is paid by Regulus Therapeutics, Inc. to provide investor relations services, and its employees or members of their families may from time to time own an equity interest in companies mentioned herein.

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