Trontinemab

Jonathan Violin loves a reverse merger, and so does Paragon Therapeutics. Violin is taking Korsana Biosciences’ fight against Alzheimer’s public. Korsana will gain access to more capital as it rides the tailwinds of Roche’s similar blood-brain barrier antibody. Korsana will take Cyclerion Therapeutics’ place on the Nasdaq in a deal that also includes a $380 million financing, the companies said Wednesday. It marks the end of Cyclerion, which spun out of Ironwood in 2019 , experienced multiple clinical setbacks , sold some assets to its former CEO in 2023, and then tried resurrecting itself last year with a treatment-resistant depression drug from MIT that was slated to enter Phase 2 this year. Cyclerion will rebrand to Korsana and trade under the ticker “KRSA” when the deal closes, slated for the third quarter. Cyclerion shareholders will get a 1.5% sliver of the combined company. Backers of the concurrent financing include a who’s who of investors in similar deals: Fairmount, Venrock, TCGX, Forbion, RTW, General Atlantic, RA Capital and about 10 others. It’s a rinse-and-repeat trend for Paragon Therapeutics, the biologics startup incubator that has revealed seven companies to date, such as Apogee and Jade. Violin forged a reverse merger for his last Paragon bet, the PD-1xVEGF contender Crescent Biopharma , with GlycoMimetics in 2024. He left for Korsana last year, but remains on the Crescent board. Crescent had come out of stealth in conjunction with its reverse merger announcement . This time around, Violin had about six weeks between a $150 million unveiling and going-public party. “We just wanted to announce ourselves, to come out of stealth and plant our flag on the playing field here,” Violin said in an interview with Endpoints News . “It had great responses in terms of potential job candidates, potential trial investigators. It’s really been nice to be able to talk about the company.” The reverse merger decision came after a swell of investor interest, Violin said, and that route allows for an “accelerated way to get a company public.” A few other reverse mergers have been announced recently, including Candid Therapeutics ’ plan to replace Rallybio’s Nasdaq spot. Korsana’s $150 million Series A in February was slated to fund operations into 2028, Violin said at the time. Now, Korsana expects to have enough money to get into 2029, which means it has plenty of runway beyond clinical trial data anticipated in 2027. Korsana is working on a shuttled monoclonal antibody that goes after amyloid beta, the nasty plaque that is one of the leading targets in the Alzheimer’s field. The goal is to get across the blood-brain barrier to have better effect on taming the memory-robbing disease and calm concerns about side effects. The company expects Phase 1 healthy volunteer data in the middle of next year. By the end of 2027, it wants interim data for its antibody KRSA-028 that show how well it does at clearing out the amyloid buildup. Roche’s candidate, trontinemab, is viewed as the frontrunner in the next wave of Alzheimer’s medicines. The Swiss drug giant took trontinemab, which is delivered by IV, into a couple of Phase 3 trials last year. Korsana is taking a subcutaneous approach. Trontinemab “is not the end of the road — we do not think it’s the best you can do for these patients,” Violin said in an interview with Endpoints in February. On Wednesday, Violin said KRSA-028’s “architecture” as a bispecific antibody “looks kind of like trontinemab,” but preclinical studies so far have shown that its performance is “quite differentiated.” Trials in humans will have to prove that out. Biogen and Eisai’s Leqembi and Eli Lilly’s Kisunla were approved in recent years for Alzheimer’s, ending a “graveyard” period for treatments in the space, Violin said in February. But those medicines can come with brain swelling and bleeding risks. The goal at Korsana is to lower the rates of those safety concerns, called ARIAs, he said. Korsana eventually wants to tackle other neurodegenerative diseases as well. There are discovery-stage projects in the works that Violin won’t talk about publicly just yet.

Biologics maker Paragon Therapeutics has spun out its seventh biotech startup, this time in pursuit of Roche in the fight against Alzheimer’s. Like Roche with trontinemab, Korsana Biosciences is attempting to deliver an antibody that shuttles across the blood-brain barrier to thwart the advancement of the memory-robbing disease. Korsana disclosed its lead asset Wednesday along with the news that it raised a $150 million Series A in September to help get to early clinical data. Investors included Fairmount, Venrock Healthcare Capital Partners, Wellington Management, TCGX, JP Morgan Life Sciences Private Capital, Janus Henderson Investors and Foresite Capital. Sanofi’s venture arm, one of the most active biotech investors of late, also took part. The nine-figure Series A marks at least the 15th megaround that private biotech startups have disclosed so far this year. The Waltham, MA-based startup was seeded with $25 million in 2024. The biotech’s battle against Alzheimer’s is much further behind than Roche’s trontinemab program, which is seen as a leading shot in the next wave of Alzheimer’s treatments and entered a set of large Phase 3 trials last year. Trontinemab “is not the end of the road — we do not think it’s the best you can do for these patients,” Korsana CEO Jonathan Violin said in an interview with Endpoints News. Korsana anticipates entering Phase 1/2 with its candidate KRSA-028 around the end of this year or early next year. It expects Phase 1 healthy volunteer results in mid-2027 and then initial data on KRSA-028’s amyloid plaque-clearing capabilities around the end of that year. The nimble 17-employee startup is betting one of its advantages will be a delivery route that eliminates the need to go to infusion centers, Violin said. Korsana is cooking up a subcutaneously delivered medicine, whereas Roche is testing an IV-formulated antibody. Korsana also hopes to tamp down on concerning side effects that have affected the inaugural class of approved amyloid-targeted medicines, namely Eli Lilly’s Kisunla and Biogen and Eisai’s Leqembi. While those treatments ended a bleak “graveyard” period for Alzheimer’s drug development, they can carry the risk of concerning side effects known as amyloid-related imaging abnormalities, which can signal brain swelling and bleeding. ARIAs are a “challenge for anyone to contemplate,” Violin said. That’s one way that trontinemab has changed the game so far in clinical testing. “The data that Roche has released is compelling, not only to take less drug, but plaques are cleared much more quickly, much more robustly and the rate of ARIA is substantially diminished,” Violin said. Other companies want to join Roche in the brain-shuttle arena. AbbVie acquired Aliada for $1.4 billion in 2024. Novartis has launched a broad approach through pacts with SciNeuro , Sironax and BioArctic . The latter is also teaming with Bristol Myers Squibb and Eisai . Roche itself is doubling down on the blood-brain-barrier approach with Manifold Bio , among others. With the competitive pressure dialed up, Korsana is staying relatively quiet on development plans, including which stage of Alzheimer’s progression it intends to attack and what type of treatment course it’s eyeing. Leqembi is meant to be taken chronically, while Lilly’s Kisunla is supposed to be stopped after amyloid plaques sink to a certain level. The best data so far are in mild cognitive impairment, but some analyses suggest that “earlier intervention is better,” Violin said. “We’ll see some data readouts from companies like Lilly before we need to make decisions.” Kisunla is in a Phase 3 trial of patients with preclinical Alzheimer’s. Korsana’s existing funds will get the startup past its early clinical data readouts, Violin said. The company’s runway goes into 2028. With the padded reserves, Korsana can remain “opportunistic” on its next financing steps, Violin said. Other Paragon spinouts made quick leaps onto public markets. Spyre Therapeutics , Oruka Therapeutics and Crescent Biopharma all announced reverse mergers at the time of their unveilings. (Violin was CEO of Crescent when it decided to jump onto the Nasdaq.) Another Paragon offshoot, Jade Biosciences , went the reverse merger route just a few months after disclosing its launch. Apogee Therapeutics took a traditional IPO path. All of those companies have done private placements or additional financings since going public.