Alnylam Pharmaceuticals, Inc.

iStock, Alona Horkova Already sky high after the success of its limb-girdle muscular dystrophy therapy, reported on Monday, BridgeBio’s shares rose nearly 8% more as encaleret balanced calcium levels in patients with a genetic thyroid disorder. Two days after BridgeBio reported the success of a limb-girdle muscular dystrophy therapy, the genetic disease biotech is back with Phase III results showing that the small molecule therapy encaleret corrected calcium levels in patients with another rare disease called autosomal dominant hypocalcemia type 1. The main goal of the study was to reach serum and urine calcium levels within a target range. BridgeBio reported on Wednesday that 76% of patients who received encaleret reached the target at week 24 compared to 4% who received standard of care. Analaysts at Mizuho said the results have exceeded investor and the company’s expectations, writing in a note to investors on Wednesday morning that “Encaleret comfortably achieved the upside case scenario.” The results also bested previous Phase II results that showed a 69% achievement of target serum and calcium levels—a major achievement as Phase III results are typically worse than Phase II, Mizuho noted. Already sky high after the success of BBP-418 in limb-girdle muscular dystrophy (LGMD) reported on Monday, BridgeBio’s shares rose nearly 8% more to just under $70 apiece in pre-market trading Wednesday. The company’s stock has risen 18% in five days. Autosomal dominant hypocalcemia type 1 (ADH1) is an inherited type of hypoparathyroidism caused by a variant in the calcium-sensing receptor (CASR) gene, leading to an imbalance in calcium in the bloodstream and urine. The condition can cause muscle cramping and spasms, seizures and kidney failure. Patients are typically treated with calcium supplements and active vitamin D. The Phase III CALIBRATE study of 70 adult patients tested whether encaleret could increase calcium in the blood and maintain levels of endogenous parathyroid hormone (PTH), which is decreased in hypoparathyroidism. The drug did both, while also decreasing levels of calcium in the urine. On a key secondary endpoint, 91% of patients taking encaleret achieved intact PTH at week 24. Mizuho also noted that encaleret acted quickly, with 71% of participants achieving target values by day three after receiving the drug. That number reached 98% by week 20. BridgeBio said that encaleret was well tolerated with no discontinuations; 97% of participants opted to continue on into a long-term extension of the study. Mizuho said the majority of treatment-emergent adverse events were mild to moderate, with most of the serious cases appearing in the standard of care arm. Analysts at Jefferies, writing in their own note Tuesday, said there were “no surprises” from the safety data. The company plans to take the therapy to the FDA for an approval application in the first half of 2026. Jefferies believes this filing plan could suggest an approval in early 2027 and, given that BridgeBio has already held multiple meetings with the FDA, an indication covering patients 16 years and older is likely. While that application proceeds, BridgeBio will continue studying the medicine in chronic hypoparathyroidism and pediatric ADH1. Mizuho expects encaleret to bring in about $750 million in peak sales in ADH1, while Jefferies puts the figure higher at $1 billion or more. BridgeBio has said that the population of symptomatic patients is about 9,000 in the U.S., with about 3,000 of those diagnosed. A Good Week For BridgeBio The results are BridgeBio’s second Phase II win of the week. On Monday, the California biotech announced that the oral small molecule BBP-418 doubled a key biomarker in LGMD that indicates muscle stabilization. A secondary endpoint showed that the drug reduced another biomarker that indicates muscle damage. Just like with encaleret, analysts heralded the results as better than expected. Elsewhere, BridgeBio is marketing Attruby, which was approved in November 2024 to treat transthyretin amyloid cardiomyopathy (ATTR-CM). The therapy landed in a crowded market that includes Pfizer’s Vyndaqel and Alnylam’s Amvuttra. But the biotech’s oral offering has held its own, notching $71.5 million in sales in the second quarter thanks to 3,751 unique patient prescriptions in the U.S. Analysts are expecting to see growth when BridgeBio reports third quarter numbers on Wednesday afternoon. Jefferies predicts sales of $102 million. Jefferies also suggests that Attruby could become “a first-line $4 billion+ pill.” BridgeBio believes the therapy is tapping into a $20 billion market opportunity, according to slides from the company’s second quarter earnings presentation.

Studies of lonvoguran ziclumeran, Intellia Therapeutics’ other clinical-phase candidate, are continuing.\n Intellia Therapeutics has temporarily paused dosing and screening in a pair of phase 3 trials in response to a liver safety signal. Shares in Intellia fell 44% to $14.34 in early trading Monday.The pause affects trials of Intellia’s nex-z, a CRISPR therapy designed to inactivate the TTR gene, in two sets of patients with transthyretin amyloidosis (ATTR). One trial is targeting ATTR with cardiomyopathy (ATTR-CM). The other trial is focused on ATTR with polyneuropathy (ATTR-PN).Intellia paused both trials after receiving a report of grade 4 liver enzymes and increased total bilirubin in a patient in the ATTR-CM trial. The patient was hospitalized, is being closely monitored and is undergoing treatment, according to the biotech.The biotech has reported elevated liver enzymes in nex-z recipients in the past. As Intellia CEO John Leonard, M.D., told analysts on a call to discuss the update, a pause was needed this time because the combination of liver enzymes and total bilirubin above the threshold met the stopping criteria. Leonard said the elevated liver enzymes and bilirubin “would meet the traditional definition of Hy\'s law,” a rule of thumb for assessing the risk of drug-induced liver injury.Intellia is now working to develop a strategy that will allow it to resume enrollment. With the biotech only receiving news of the adverse event Friday, management is still early in the process of figuring out the causes of the liver safety signal.“At this point, it\'s just premature to comment on any sort of predictors or patient populations at risk,” Leonard said. “Obviously, we\'re looking into that, and we\'re assembling a set of questions to pursue with our [data and safety monitoring board] and related parties.”The patient had elevated liver enzymes more than three weeks after receiving nex-z. Leonard said there are similarities between the timing of the case and another patient who had asymptomatic elevated liver enzymes earlier in the phase 3 program. The patient who was hospitalized appears to have “a more pronounced manifestation” of the changes seen in the other patient, the CEO said. The lag between administration of nex-z and the emergence of elevated liver enzymes suggests the lipid nanoparticles (LNPs) used to deliver the therapy are unlikely to have caused the adverse events. Patients can have small increases in liver enzymes in the day or two after receiving LNPs. The timing led Leonard to speculate that Intellia is facing another problem.Leonard thinks the problem is limited to Intellia’s TTR program. Studies of lonvoguran ziclumeran, the biotech’s other clinical-phase candidate, in patients with hereditary angioedema are continuing. It is unclear how long it will take Intellia to get the TTR trials back on track. Leonard said he can only speculate on the duration of the pause but added that work on the resolution will certainly take “some weeks.” Any delay will push back Intellia’s potential entry into a space served by Alnylam, BridgeBio and Pfizer. If eventually approved, nex-z could be a one-time alternative to existing therapies.

A transatlantic drug developer with five projects in the oven, including two in clinical testing, has raised $157 million to try and push forward several advances in treating disorders related to blood clotting. The new money could get the US and Danish startup, called Hemab Therapeutics, close to the FDA’s doorstep with prophylactic treatments for Glanzmann thrombasthenia, factor VII deficiency and von Willebrand disease. “There’s probably more than 30 approved drugs for hemophilia A and B. There are zero approved drugs for Glanzmann. There are zero preventative drugs for factor VII. There are no new modern, subcutaneously-administered preventative therapies for Von Willebrand disease,” Hemab CEO Benny Sorensen said in an interview with Endpoints News. “I can go down the list of other zeros,” Sorensen said. “So the time is really now to try to build a company like Hemab.” The round announced Monday was well above the approximately $100 million it had originally set out to raise, according to Sorensen. The new money will get three therapies to key clinical readouts en route to Hemab’s mission of becoming the “ultimate coagulation disorder” biotech, he said. It last raised a $135 million Series B in 2023. Monday’s fundraise continues a string of good news for private biotechs. This marks the 15th biotech megaround of the past four weeks, according to an Endpoints tally. It’s also not the only recent large raise in Hemab’s area: Last month, Star Therapeutics announced a $125 million Series D round for its Phase 1/2 drug to treat von Willebrand disease. Sorensen said it’s “great for patients that there’s innovation and there’s competition because the winners, hopefully, will then be the patients.” With 60 employees split evenly across Cambridge, MA, and Copenhagen, Hemab has been able to get two experimental medicines into the clinic already. In the lead is sutacimig, a bispecific antibody that has potential in a variety of indications. One part of the antibody binds to endogenous factor VIIa, while the other arm latches onto TLT-1. The subcutaneously-delivered antibody is slated to enter a global Phase 3 next year for Glanzmann thrombasthenia, Sorensen said. The condition can lead to life-threatening bleeding episodes. In a Phase 2 of 34 patients, sutacimig led to “well over 50% reduction in annual treated bleeds,” the CEO said. Hemab will also have data from a Phase 2 of sutacimig in factor VII deficiency next year, he said. Behind that is HMB-002. The monovalent antibody targets the C-terminal CK domain of von Willebrand factor, which plays a role in bleeding control. A Phase 2 in von Willebrand disease will wrap up next year, Sorensen said. The condition is “probably the most prevalent bleeding disorder in the world,” he said. “We are pursuing a really simple, intuitive therapeutic hypothesis where if you have low levels of von Willebrand factor and factor VIII, we are aiming to increase those levels toward the normal reference range,” Sorensen said. A third asset for an undisclosed condition will enter human trials next year. As part of its 2025 road map, it also has “a fourth and a fifth project that are brewing in our laboratories,” Sorensen said. Details on those programs will likely come out next year. With five programs in its pipeline, Hemab is going against the grain of most other startups. Over the past few years, many private biotechs have prioritized their R&D around one or two assets to conserve cash. But with a specific focus on bleeding disorders, Hemab has been able to build out an “an unbelievably concentrated domain expertise in clotting,” Sorensen said. He’s been working in blood clotting since he was a medical student, then at Alnylam, where he contributed to anti-thrombin medications. Hemab’s chairman is former Alnylam CEO John Maraganore. “The Hemab team has been involved with more than 60% of all approved drugs in blood clotting,” Sorensen said. Maraganore was behind the anticoagulant branded as Angiomax. With that expertise, the company could go all the way to the market on its own. Sorensen pointed to last month’s hiring of operating chief Anant Murthy as being able to help take its pipeline “from development into launch.” Murthy also worked at Alnylam, among other roles at argenx, Ariad and Celgene. It also helps that Hemab has some of the biggest names in biotech investing at its side. Sofinnova Partners led the Series C. Qatar Investment Authority, Avoro Capital Advisors, RA Capital, Novo Holdings and others also took part.