Regulus and Sanofi update partnership agreement

LA JOLLA, Calif.—Regulus Therapeutics Inc. has renewed its strategic alliance with Sanofi to discover, develop and commercialize microRNA therapeutics. The joint effort will focus on a specific orphan disease, Alport Syndrome—a life-threatening genetic kidney disease with no approved therapy—and oncology targets. This is the third wave of investment by Sanofi in Regulus and its programs in an alliance that dates back to 2010, notes Regulus President and CEO Dr. Kleanthis G. Xanthopoulos. Sanofi also participated in the Regulus IPO in 2012 and has upped their ante by $10 million this time around.

Regulus will lead development of its fibrosis program targeting microRNA-21 (miR-21) for the treatment of Alport Syndrome and for its miR-21 program in oncology. “MiR21 is the ‘rock star’ of microRNA,” says Xanthopoulos. “It is overexpressed in every solid tumor we’ve looked at.” Sanofi has retained its interest in these microRNA-21 programs and has gained rights to Regulus’ preclinical program targeting microRNA-221/microRNA-222 (miR-221/222) which are overexpressed in liver tumors. Regulus is responsible for advancing the clinical candidates in these programs to proof of concept. Sanofi will have the exclusive option, exercisable after proof of concept, to take over further development and commercialization of each microRNA therapeutic program. At this stage, Regulus will have the option to co-promote any microRNA therapeutic product in the United States.

“The renewal of our strategic relationship with Sanofi further underscores the commitment of both companies to realize the tremendous promise of RNA therapeutics and the possibility to transform the field of drug discovery by targeting microRNAs,” said Xanthopoulos. “We believe that Regulus’ microRNA therapeutic platform, coupled with our focus on orphan diseases and oncology indications, combine perfectly with Sanofi’s resources and their proven capabilities as a global healthcare leader to bring innovative medicines to patients in need. We look forward to advancing our programs together and building a meaningful clinical portfolio.”

The refocused relationship allows Sanofi and Regulus to continue to collaborate on several meaningful microRNA therapeutic programs, with a greater focus on orphan diseases and oncology. Under the original agreement from 2010, Sanofi had rights on up to four microRNA targets, which included Regulus’ lead fibrosis program targeting miR-21. In 2012, the companies expanded the alliance to collaborate on an oncology program targeting miR-21. In 2013, the companies entered into an option letter agreement to allow for negotiation of the extended strategic alliance just announced. Sanofi retained its interest in developing miR-21 therapeutics for fibrosis and oncology indications and now has opt-in rights to Regulus’ miR-21 and miR-221/222 programs. If Sanofi chooses to exercise its option on any of these programs, it will reimburse Regulus for a significant portion of its preclinical and clinical development costs. Regulus continues to be eligible to receive royalties on microRNA therapeutic products commercialized by Sanofi.

The announcement by Regulus that RG-012, its candidate Alport Syndrome product, inhibits miR-21 upregulation associated with fibrotic disease in animal models, both decreasing the rate of renal fibrosis and increasing lifespan by 50 percent, generated positive reaction.

Dr. Jim Birchenough of BMO Capital Markets Corp., for one, greeted the news with optimism. “We reiterate our ‘outperform’ rating on shares of RGLS following advancement of RG-012 toward clinical development for Alport Syndrome. Biologic rationale and preclinical data are compelling and with a planned natural history study in 3Q14, we expect significant de-risking of the program over the next 12 to 18 months. Commercial opportunity is significant with 20,000 Alport Syndrome patients in the U.S. alone, and an estimated $3 billion to $6 billion opportunity at current orphan disease pricing. While an absence of approved therapeutics has left no clear regulatory path, we believe that identification of key biomarkers and improvement in renal function, or down-staging of end-stage renal disease (ESRD) could potentially provide a path to rapid approval.”

Regulus is also developing RG-101, a GalNAc-conjugated anti-miR targeting microRNA-122, for the treatment of all genotypes of chronic hepatitis C virus infection, including tough-to-eradicate genotype 3. Once-a-month dosing is planned with a four-month course of therapy on top of oral anti-virals. In all, Xanthropoulus expects the company to have two programs in the clinic within the next 12 months.

In addition to its relationship with Sanofi, Regulus has formed strategic alliances with AstraZeneca in metabolic disorders and oncology, and GlaxoSmithKline targeting immuno-inflammatory diseases.

MicroRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, which do not encode proteins but instead regulate gene expression. More than 500 microRNAs have been identified in the human genome, and over one-third of all human genes are believed to be regulated by microRNAs. MicroRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis and metabolic diseases. Regulus believes that microRNAs are clinically relevant therapeutic targets and may be ideally suited as biomarkers for these disease states and others. MicroRNAs have been detected in bodily fluids such as blood, and emerging data has demonstrated that microRNA signatures in blood can mimic the expression profile observed in disease tissues. Regulus has a rich intellectual property estate and oligonucleotide technology know-how and believes that microRNA biomarkers may be used to select optimal patient segments in clinical trials and to develop prognostic and predictive markers that can help monitor disease progression or relapse.