Dicerna Pharmaceuticals, Inc.

Since stepping down as CEO of Alnylam Pharmaceuticals three years ago, John Maraganore has lent his talents widely, joining the boards of up-and-coming biotechnology companies, advising them on strategy and allying with some of the venture firms that back those young drugmakers.His latest role returns him to his Alnylam roots. On Tuesday, City Therapeutics launched with a plan to build the next generation of the RNA interference medicines Alnylam pioneered. Maraganore, who co-founded City with a group of venture capitalists, scientists and other Alnylam veterans, will serve as the biotechs executive chair.At Alnylam, we launched the birth of RNAi therapeutics as a new class of medicines, Maraganore said in a statement announcing Citys debut. We see the potential for RNAi to emerge as the next major category of high-impact medicines, rivaling if not exceeding the success of monoclonal antibodies.New innovation is needed to realize this future, and we believe City Therapeutics can lead this next chapter, he added.City plans to innovate in several ways, including by tweaking the components of the biological process by which RNA interference, or RNAi, works. Typically, RNAi is described as a technique to silence genes. It does so via small, interfering strands of RNA that trigger cleavage of the messenger RNA instructions cells use to produce proteins.City aims to design new kinds of RNAi triggers that similarly spark mRNA cutting, but are smaller and more potent. One example is what City terms cleavage-inducing tiny RNAs, the acronym for which led to the biotechs name.The startup also aims to design targeting molecules, or ligands, that enable the delivery of these engineered RNA strands to more types of cells and tissues. (The approved RNAi medicines that Alnylam and rival Dicerna Pharmaceuticals have to date developed are all aimed at the liver.)To get started, City has $135 million in funding from a large syndicate of investors that includes Arch Venture Partners, an early investor in Alnylam. Also backing City are Fidelity Management & Research, Invus and Regeneron Ventures, along with several other firms.The time to re-enter the RNAi revolution is now, and our investment in City Therapeutics is based on our conviction that RNAi therapeutics will expand as a major category of breakthrough medicines, said Robert Nelsen, a managing director and co-founder of Arch, in a statement.City didnt disclose which diseases it will target, but expects to begin clinical testing for its first program at or around the end of next year. The company hopes to advance one or two new drugs into the clinic each year after that.Its not the only biotech startup setting out to improve on RNAi medicines. On Monday, Judo Bio launched with plans to bring RNAi drugs to the kidney by using what it calls ligand-siRNA conjugates. Maraganore is also on Judos advisory board. '

Dive Brief:A new biotechnology company called Judo Bio is taking a strike at kidney diseases, armed with $100 million and a RNA drug platform it claims can get to targets that historically have been challenging for researchers to hit.Formed three years ago, Judo is backed by a handful of investors that include Atlas Venture, which incubated the startup and co-led its Series A, as well as The Column Group and Droia Ventures.With its technology, Judo is following in the footsteps of Alnylam Pharmaceuticals, which pioneered use of a biological process called RNA interference to make a new class of drugs. Unlike Alnylams first medicines, which are directed at the liver, Judo claims it can reliably sneak its RNA medicines into the kidney.Dive Insight:First discovered in 1998, RNA interference gave drugmakers a tool to silence genes that encode disease-causing proteins. In the nearly three decades since, Alnylam has used that tool to develop five approved medicines for a range of rare and common diseases. (A sixth, from Novo Nordisk-owned Dicerna Pharmaceuticals, is also approved.)Those medicines work via whats known as small interfering RNA, or siRNA, which can mute messenger RNA and thereby prevent problematic proteins from being made by a cell.Judo sees itself as a successor of sorts. Its leadership includes Alnylam veteran Alfica Sehgal, who now serves as the startups chief scientific officer, while John Maraganore, Alnylams former CEO, sits on its advisory board.The companys platform is built around so-called ligand-siRNA conjugates, which pair the gene silencing nucleic acid with a targeting molecule. Judos ligands shuttle the RNA payload to specific types of kidney cells, where they bind to a receptor known as megalin that helps cells absorb vitamins and fats.Bound to megalin, Judos drug is ingested by the cell and, once inside, works to silence mRNA expression of solute carrier proteins. These proteins typically act as transporters and their dysfunction is linked to a range of diseases.According to Rajiv Patni, Judos CEO, using a proven mechanism like siRNA allowed the company to pursue more challenging drug targets like those in the kidney.The kidney is a huge risk in part but not entirely because of its complexity, Patni said. As a drug developer, you're always thinking about a tissue target that is the holy grail.The kidney's complexity is also why Judo chose to focus on the organ. It's where blood is filtered and, while other drugs can reach the organ, theyre typically excreted without any helpful effect.The company has not disclosed disease targets, but Patni says Judo is looking at systemic diseases such as diabetes and hypertension, as well as kidney-specific conditions.Judo shares its name with the form of martial arts known for taking a weakness and turning it into a strength, said Sehgal, the Alnylam vet. One of Judos primary moves, a strike, is also the acronym for the companys platform, which is being developed to knock down certain genes via the kidney.The company is presenting preclinical data at the Oligonucleotide Therapeutics Societys annual meeting this week that it says show ligand-siRNA conjugates can durably knock down targeted gene expression. '

Novo and Lilly/Taylor Tieden for BioSpace Novo Nordisk and Eli Lilly are expected to rule the obesity market for a few more years without much challenge. To ensure they stay there as competition enters, the companies are spending billions in licensing and M&A deals. Novo Nordisk and Eli Lilly are undoubtedly at the top of the weight loss market. With $1.7 billion in second-quarter sales recorded for Novo’s Wegovy and $1.2 billion for Lilly’s Zepbound, the companies are raking in profits. The two behemoths are likely to remain in that spot until competitors begin to arrive on the market around 2026, according to a report from Pitchbook and Morning Star issued on September 9. But the next wave of drugs, coming from companies like Terns Pharmaceuticals, Structure Therapeutics, Pfizer and Amgen, look like they could beat the current offerings. All these companies could come together to battle for a market Pitchbook estimates could reach $200 billion annually by 2031. But Lilly and Novo are not standing idly by. They’ve been scooping up companies and making deals, diversifying their bets on obesity treatments. And both pharmas are highly anticipated to make further acquisitions in the space, according to the report. Both have also taken smaller bites with licensing deals to explore new targets or next-generation GLP-1 approaches. Obesity is a key investment focus for Novo, executives said during an investor day presentation in March. Of the two, Novo has been the most prolific on the business development stage by far, with 37 partnerships focused on cardiometabolic diseases and obesity, according to the presentations. The company is specifically focused on finding new mechanisms of action. For example, Novo is heavily investing in siRNA technology for a number of therapy areas, the majority of which are in diabetes and obesity. The company is also building out internal capabilities in proteins, peptides and monoclonal antibodies, while partnerships and acquisitions are adding small molecule options to its obesity pipeline. Meanwhile, Lilly allocated $1.4 billion for business development overall, including milestones, closed acquisitions and equity investments in the first half of the year. Another $4.4 billion went to total R&D; the pharma has 11 new molecules in development for obesity, including a robust late-stage program and nine trials currently running. “In obesity, our strategy is to comprehensively address this global public health crisis, pursuing opportunities against every rational mechanism, indication, and dosage form,” said CEO David Ricks on the company’s second quarter earnings call in early August. Read on for more on the deals that Novo and Lilly hope will keep them at the top of the obesity world. Lilly: Haya Therapeutics Partnership Date: September Value: Up to $1 billion Asset(s): Multiple RNA targets Most recently, Lilly put up to $1 billion on the line —although the exact financial breakdown was not disclosed—to work with Haya Therapeutics earlier this month. The Swiss biotech is using an RNA-guided genome platform to target obesity and other metabolic conditions. Haya will conduct drug discovery to find multiple tissue-, disease- and cell-specific long non-coding RNA targets (lncRNA) to develop into therapeutics. Specifically, Lilly is looking for treatments with better efficacy and less toxicity than existing options for weight loss. That’s, of course, the holy grail. While Wegovy and Zepbound are undeniably effective, they are associated with gastrointestinal side effects and muscle loss. The next generation of therapies will seek to imnprove on those two measures, but also on delivery. Novo: Metaphore Partnership Date: May Value: $600 million Asset(s): Two GLP-1 receptor agonists Novo has worked with venture creation firm Flagship Pioneering since 2022 (see below), but in May, they doubled down. The Danish pharma signed a deal with one of Flagship’s portfolio companies, Metaphore Biotechnologies, to develop two next-generation GLP-1 receptor agonists. The deal included up to $600 million in upfront, development and milestone payments. Novo plans to use Metaphore’s MIMIC platform, which can copy the interactions between molecules to develop therapeutics to activate the GLP-1 receptor and related pathways. The deal also includes “a novel machine learning approach to obesity management,” the companies said in announcing the deal. Novo: Catalent Acquisition Date: February Value: $16.5 billion Asset(s): Three fill finish sites This list would not be complete without this outlier, Novo Holdings’ $16.5 billion acquisition of contract development and manufacturing organization Catalent. This deal does not bolster Novo’s pipeline, exactly, but will certainly support the company’s obesity-driven revenue. Novo Nordisk’s holding company took control of three of Catalent’s manufacturing sites to bolster production of the blockbuster drugs Ozempic for diabetes and Wegovy for weight loss. Both use the same active ingredient, semaglutide. The troubled manufacturer had revenue losses of $539 million in 2023 as demand for COVID-19 vaccines and treatments waned, plus debt of more than $5 billion. The company had also faced multiple quality control concerns. Novo: EraCal Licensing Deal Date: January Value: $255 million Asset(s): Oral small molecule program Sometimes, you have to dig a little deeper into existing partnerships. Novo did exactly that, adding on a new mechanism of action in obesity through a $255 million licensing deal with Swiss biotech EraCal Therapeutics signed in January. The deal granted Novo exclusive rights to EraCal’s oral small molecule program, which aims to control appetite and body weight to treat obesity. The two companies had been working together since 2022, when they entered into a collaboration to find targets for food intake regulation and other metabolic phenotypes. The partnership examined zebrafish larvae to find new targets to act against obesity. Novo: Omega Therapeutics Licensing Deal Date: January Value: $532 million Asset(s): Epigenomic controller program Novo inked the first of two licensing options in obesity this year with Flagship in January, starting with Omega Therapeutics . The pharma opted in on a program designing an epigenomic controller designed to enhance metabolic activity, with the hope of developing a new treatment for obesity management. The agreement also included a second opt-in for a metabolic dysfunction-associated steatohepatitis (MASH) therapy with Flagship’s Cellarity. Flagship’s Pioneering Medicines and Novo will jointly support the programs through preclinical work and then Novo will advance them into the clinic and reimburse R&D costs. Novo pledged $532 million upfront for each agreement in upfront, development and commercial milestone payments. Lilly: Fauna Partnership Date: December 2023 Value: $494 million Asset(s): Multiple weight loss targets Lilly looked to the animal kingdom for some new weight loss targets in a deal signed with Fauna Bio worth up to $494 million in December 2023. The multi-year partnership will see the two work on finding new targets for weight loss drugs using Fauna’s artificial intelligence platform called Convergence. The platform analyzes genomic data from 452 animal species and tissues along with human data to find novel drug targets. Lilly: BioAge Trial Partnership Date: October 2023 Value: Not disclosed Asset(s): Azelaprag Lilly’s partnership with BioAge stands out a bit on this list. The companies agreed to work together on a clinical trial pairing the biotech’s apelin receptor APJ agonist azelaprag with Lilly’s Zepbound. The hope with thethis clinical trial is that the combo will boost the weight loss potential of Lilly’s mega-blockbuster. These kinds of clinical trial supply agreements happen all the time, but Lilly is conducting the research through its independent clinical development organization called Chorus. The unit works with biotechs to develop assets through clinical proof of concept. Lilly put more skin in the game by also participating in BioAge’s series D financing in February. BioAge raised $170 million with backing from RA Capital, Cormorant, SV Health, Lilly and Amgen. The biotech has since filed to go public and is seeking up to $153.3 million, according to a September 18 SEC filing . Novo: Embark Biotech Acquisition Date: August 2023 Value: $507 million Asset(s): Embark Biotech, assets from Embark Laboratories Novo did a double deal with Embark Laboratories in August 2023, fully acquiring Embark Biotech and signing a three-year research collaboration with the lab. In Embark Biotech, Novo scored a metabolic program for up to $507 million. And for the research collaboration, Novo gained an option to acquire selected assets retained by Embark Laboratories based on Embark Biotech discoveries in obesity, type 2 diabetes and other indications. Novo: Inversago Pharma Acquisition Date: August 2023 Value: $1.1 billion Asset(s): Inversago Pharma Novo is already seeing the fruits of its $1.1 billion buyout of Inversago Pharma , a Canadian company that had been developing novel cannabinoid receptor 1 (CB1) receptor-based therapies. The August 2023 deal brought in a new modality for Novo to explore in its ever-expanding obesity pipeline. Just last week, the company revealed the first results for one of the candidates, monlunabant, showing that the oral CB1 inverse agonist cut weight by 15 lbs after 16 weeks. The data reveal was low on detail, however, and Novo did not present the weight loss as a percentage of bodyweight, which has been common in these types of trials. Novo also noted some “mild to moderate neuropsychiatric side effects,” such as anxiety, irritability and sleep disturbances. This class of drugs has been known to cause neuropsychiatric issues, including suicidality, so Novo said it intends to work with the dosing in future trials, after proving that monlunabant can in fact reduce weight. Lilly: Versanis Bio Acquisition Date: July 2023 Value: $1.925 billion Asset(s): Versanis Bio In July 2023 , Lilly swept in and bought out Versanis , a biotech that had formed around a Novartis castoff, for $1.925 billion. At the center of the deal is bimagrumab , a monoclonal antibody that aims to reduce fat without affecting muscle mass. Novartis developed the therapy in muscle disorders but studies failed to show improvement in patients’physical function. Researchers did, however, note that people taking the drug lost weight. Fast-forward to the weight loss craze that is sweeping the pharmaceutical industry, and Lilly jumped on Novartis’ discard through the nearly $2 billion outlay. Bimagrumab is being tested in the Phase IIb BELIEVE study for adults to achieve and maintain fat loss and a healthy body composition. Completion is expected in mid-2025, according to ClinicalTrials.gov . Novo: Flagship Partnership Date: May 2022 Value: Not disclosed Asset(s): Multiple company partnerships Why work with one company when you could work with 41? That’s what Novo did in signing a partnership with prolific biotech creator Flagship Pioneering in May 2022. The deal focused on cardiometabolic and rare diseases, providing Novo with access to the platforms developed by Flagship’s many companies. Novo offered funding for initiated research programs and will have an exclusive option on any programs licensed from the deal. The goal was to kickstart three to five programs within the first three years. The deal has since produced collaborations with Metaphore and Omega in obesity (see above), plus Cellarity in MASH. Novo: Dicerna Acquisition Date: December 2021 Value: $3.3 billion Asset(s): Dicerna Novo tapped into Dicerna Pharmaceuticals in 2019 to find new RNAi therapies, in a partnership that examined 30 liver cell targets that could yield new therapeutics in MASH, type 2 diabetes, obesity and rare diseases.  Satisfied with the work, Novo went all in, buying out the company entirely in November 2021 for about $3.3 billion. The first target from the original collaboration, a NASH drug, entered the clinic in 2022, but Novo was also looking to the deal to expand the company’s RNAi research. Besides obesity, Novo sees the possibility for Dicerna’s technology to find therapies for diabetes, cardiovascular disease, MASH and endocrine and bleeding disorders. Novo: Kallyope Licensing Deal Date: June 2018, September 2024 Value: Not disclosed Asset(s): Ligand for obesity This deal has a slow burn. Originally signed in June 2018 , Novo and Kallyope agreed to discover novel peptides for obesity and diabetes. No financial details were released at the time, but the deal involved an upfront fee and research support. Novo gained the rights to up to six products and offered a licensing fee if any were optioned. Kallyope is exploring the gut-brain axis, with four programs underway for metabolism. Earlier this month, we finally heard how the partnership was going . Novo exercised an option to license a ligand identified by Kallyope for obesity. Again, financial details were kept under wraps. Novo said it believes it’s found a new mechanism for obesity in the Kallyope program. Now, the Danish pharma will take over preclinical and clinical development, manufacturing and commercialization. Kallyope has received an upfront option payment and may receive additional payments down the line in development and sales milestones and royalties.