Apellis, Sobi See Potential ‘Best-in-Class’ Efficacy for Empaveli in Rare Kidney Diseases

 

Empaveli reduced proteinuria by 68% versus placebo in glomerulopathy and glomerulonephritis, an effect that was sustained through one year of follow-up.

Apellis and Sobi’s complement regulator Empaveli—sold under the brand name Aspaveli in Europe—sustained the reduction of proteinuria in patients with C3 glomerulopathy and primary immune complex membranoproliferative glomerulonephritis through one year in a Phase III trial, potentially bolstering the drug’s case ahead of a July PDUFA date.

Analysts at William Blair said in a Monday note that the new data continue to support Empaveli’s “game-changing profile” in the two rare kidney diseases.

"[Empaveli] has best-in-class efficacy that should drive significant adoption in this underserved population over time,” the analysts wrote.

In the Phase III VALIANT trial, Empaveli lowered proteinuria by 68% versus placebo at 28 weeks, an effect the partners claimed was statistically significant. Empaveli, they added, was able to sustain this benefit through one year of follow-up. Kidney function, as measured by estimated glomerular filtration rate, also stabilized in patients treated with Empaveli.

The development partners presented the data during a late-breaking session at the European Renal Association Congress.

VALIANT enrolled nearly 125 patients 12 years and up who had been diagnosed with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN)—both rare kidney diseases characterized by inflammation in the organ linked to excessive deposits of the C3 complement protein. Both diseases can ultimately lead to kidney failure in half of patients within 10 years of diagnosis.

Designed to be injected under the skin, Empaveli inhibits the immune system’s complement cascade, a part of the body’s immune system. This mechanism of action won the drug an FDA approval in May 2021 in paroxysmal nocturnal hemoglobinuria. European approval came a few months later.

Apellis, which partnered with Sobi in October 2020 to bring the drug to ex-U.S. markets, has since worked to expand Empaveli’s label. In April, the biotech announced that the FDA accepted its application to use Empaveli in C3G and IC-MPGN and granted the drug Priority Review. A verdict is expected by July 28.

Elsewhere in the kidney disease space, Otsuka also revealed promising data on Friday for its antibody therapy sibeprenlimab. Late-stage results in patients with immunoglobulin A nephropathy showed that sibeprenlimab could reduce proteinuria by 51.2% versus placebo—an effect that Guggenheim Partners called “impressive” in a Friday note. Sibeprenlimab, they continued, showed “the strongest numerical result reported to date in IgAN Phase 3 trials.”

Otsuka has yet to detail out its regulatory plans for sibeprenlimab, though the company on Friday emphasized that “proteinuria reduction is a recognized surrogate marker” and “has been used as an endpoint in IgAN clinical trials to support accelerated regulatory approvals.”

https://www.biospace.com/drug-development/apellis-sobi-see-potential-best-in-class-efficacy-for-empaveli-in-rare-kidney-diseases

Metsera Shares Rise as Monthly Weight Loss Injection Shaves Over 8% Body Weight at 36 Weeks

 

In what Guggenheim Partners called one of Metsera’s “critical program milestones” this year, its ultra-long-acting amylin injection MET-233i showed promising weight-loss over about eight months.

Metsera has once again jolted the weight loss space with Phase I results from an ultra-long-acting amylin injectable showing weight loss of 8.4% at 36 weeks. The biotech’s shares rose as much as 20% on Monday morning.

The results for the ultra-long-acting, early-stage amylin injection MET-233i had been hotly anticipated by analysts. In a Feb. 25 note to investors, analysts at Guggenheim Partners identified the early data for MET-233i as among Metsera’s most important “critical program milestones” this year, adding that the readout had the potential to “substantially de-risk the program.”

MET-233i, which Guggenheim noted is the only potential once-monthly amylin in clinical development, could also be combined with Metsera’s other pipeline assets that target GIP and glucagon, in turn opening up “pathways to differentiated products and market segmentation.”

Guggenheim estimated that the market for ultra-long-acting injectable incretin therapies could hit $19 billion by 2035.

Monday’s readout comes from a Phase I study that tested MET-233i as a monotherapy in 80 patients who were overweight or obese but who did not have type 2 diabetes. Results showed that at 36 weeks, patients treated with 1.2-mg of MET-233i saw an average weight reduction of 8.4% relative to placebo, with some individual responses reaching as high as 10.2%.

Pharmacokinetic analysis also pointed to a half-life of 19 days, which according to Metsera supports the once-monthly dosing regimen. Patients treated with MET-233i were also able to keep the weight off for more than four weeks, which is indicative of the amylin therapy’s ultra-long-acting profile, the biotech noted.

As for safety, MET-233i had a relatively clean profile, with no severe or serious toxicities to date. Gastrointestinal side effects—less common than with GLP-1s but still typical of the amylin drug class—were mild and limited to the first week of dosing, a pattern that Metsera claims is suggestive of the “rapid onset of tolerance.”

With Monday’s data, Metsera plans to continue its monotherapy study for MET-233i, for which topline findings are expected later this year. The biotech is also testing the amylin injection with its ultra-long-acting GLP-1 therapy MET-097i. Data from the combo trial could come as early as year-end 2025, or in early 2026, the company said. Guggenheim also noted that data from monthly dosing of MET-097i on its own is expected later this year or early next year, calling it a “key value-driving readout.”

Amylin Takes the Weight Loss Spotlight

Designed to be administered once a month via an injection under the skin, MET-233i is an analog of the amylin protein, a pancreatic hormone that works with insulin to slow the emptying of the stomach and lower glucose levels in the blood. Unlike the more entrenched GLP-1 drugs, amylin therapies could potentially offer several advantages, including better tolerability and lower loss of lean mass.

With this in mind, more and more biopharma players are studying amylin therapies for obesity. Leading the pack is weight loss frontrunner Novo Nordisk, which is developing CagriSema, a next-generation combination that uses its blockbuster GLP-1 drug semaglutide with the long-acting amylin analog cagrilintide.

Despite being the most mature amylin asset, CagriSema has struggled to meet the sky-high expectations of analysts and investors. In December 2024, weight-loss figures from the Phase III REDEFINE 1 study underwhelmed, with weight-loss reaching 22.7% at 68 weeks, versus a prior expectation of 25%. The blunder triggered a share selloff that wiped some $72 billion from Novo’s market cap.

In March, additional late-stage data likewise failed to make investors happy, resulting in a 7% dip in the pharma’s share price at the time.

In dissecting REDEFINE 1’s outcome, Guggenheim analysts in the February note flagged the study’s flexible dosing protocol, which they say resulted in only 56% of patients hitting the maximum dose of CagriSema. The analysts called this an “unforced error” that led to the underestimation of the full potential of CagiSema.

“However, in our view, [Novo] not only unequivocally validated the amylin mechanism in obesity, but their unforced error opened up a lane for other amylin competitors—particularly those that are differentiated like [Metsera’s] ultra-long acting MET-233i,” they wrote.

Other amylin players include Eli Lilly, which is expecting a Phase II readout for eloralintide in mid-2025, AbbVie, which bought into the space in March with a potential $2.2 billion deal with Denmark’s Gubra.

https://www.biospace.com/drug-development/metsera-shares-rise-as-monthly-weight-loss-injection-shaves-over-8-body-weight-at-36-weeks

Keros To Return $375M to Investors After Shareholder Activism, Safety Signal

 

After a major shareholder pushed back, Keros is returning half of its capital to investors in a move that Guggenheim analysts called “a positive step forward.”

A little over a week after Keros Therapeutics cut staff and pared back work on its former lead asset cibotercept on the revelation of a safety signal, the company is now giving back investors $375 million—about half of its capital.

Investors may have preferred that all the cash—about $720 million as of the end of the first quarter—be returned, but the decision is at least a step in the right direction, analysts at Guggenheim said in a Monday morning note.

The decision caps off a tumultuous period for investors. The Massachusetts biotech announced a strategic review in April that could include a sale, business combination, continued investment in the pipeline or return of capital to shareholders. In response, the biotech’s largest shareholder, ADAR1 Capital Management, sparked a revolt, urging the company to abandon all of its medicines but elritercept that was licensed to Takeda in December 2024. ADAR1 argued that the drug could achieve peak sales of $2 billion, while the other two assets—cibotercept and KER-065—had shown “alarming clinical results.” The firm urged shareholders to vote down members of Keros’ board who were up for re-election and asked the company to restructure and return capital to shareholders.

The situation escalated at the end of May after a safety signal arose in the Phase II trial of cibotercept for patients with pulmonary arterial hypertension (PAH). At the time, the PAH program was eliminated and 45% of staff were let go. Keros pledged to review further development—if any—of cibotercept.

On Friday, the effort to vote down the board members failed at Keros’ annual general meeting. The company followed up Monday with the announced plan to return capital to shareholders, which concludes the strategic review. The board will announce the specifics of the capital return at a later date.

Development of KER-065 for neuromuscular diseases will continue, with an initial focus on Duchenne muscular dystrophy, according to the board’s lead independent director, Jean-Jacques Bienaimé.

“This reflects a thorough review of our capital requirements, feedback from our stockholders, and our confidence in the potential for Keros to provide meaningful and potentially disease-modifying benefits to patients,” Bienaimé said in a statement.

Guggenheim shrugged off the decision to shift the spotlight to KER-065, “to which we currently do not attribute any revenue in our company model.” The company had been expected to start a Phase II trial in DMD in the first quarter of 2026, according to a May 7note from Guggenheim .

Keros still has future revenue opportunity from the activin receptor type IIA (ActRIIA) fusion protein elritercept, which Takeda licensed for development in myelodysplastic syndromes and myelofibrosis. The deal gave Keros $200 million through an upfront payment, which was recorded in the first quarter of this year, according to a company earnings release. The partnership also includes $1.1 billion in milestones and royalties.

Keros’ shares have declined 70% in the past year from a peak of $70 to $14.37 as of Monday morning.

https://www.biospace.com/business/keros-to-return-375m-to-investors-after-shareholder-activism-safety-signal

"We'll Do It Ourselves!" Dutch Vigilantes Stop Cars At German Border In Protest Over Illegal Migration

 by Thomas Brooke via Remix News,

A group of Dutch citizens staged an unauthorized border control operation this weekend between Ter Apel and the German village of Rütenbrock, citing frustration with what they describe as uncontrolled illegal immigration.

Wearing reflective clothing and wielding torches, the group of around 12 men began stopping vehicles on Saturday evening along the N366, a key route between Germany and the Netherlands.

The vigilantes, who pulled cars over and even inspected trunks, say they took action because authorities are failing to secure the border and stem the flow of asylum seekers entering the country. “Nothing is happening. Then we’ll do it ourselves,” said one activist, as cited by Algemeen Dagblad.

The action, although brief, drew sharp criticism from police and government officials. The municipality of Westerwolde and Dutch police released a joint statement declaring that “citizens are forbidden to stop cars” and that such actions “create enormously dangerous situations” and are “really unacceptable.” The vigilantes are believed to have violated road traffic laws, though it is unclear whether any formal charges will be brought.

One vehicle stopped by the group turned out to be a German police van. The officers promptly ordered the group to leave German soil, threatening to tow their vehicles if they did not comply. The activists relocated their checkpoint to a parking lot on the Dutch side of the border and continued stopping traffic from Germany.

The group, reportedly organized via Facebook, primarily includes residents from the municipality of Westerwolde.

Outgoing Justice and Migration Minister David van Weel, of the center-right VVD, responded by urging the group to stop. “I understand the frustration, but I really call on this group not to do this,” he said. “Let the police and military police do their job and abide by the law.” Van Weel acknowledged the Netherlands “cannot handle the current influx,” but insisted that border enforcement must remain the responsibility of the authorities.

Mayor Jaap Velema of Westerwolde expressed sympathy for the frustrations, citing “the lack of solutions to the crisis in asylum reception,” but warned: “This is not the way to express frustrations. We can’t all drive through red lights either.”

Geert Wilders, leader of the anti-immigration PVV party, praised the citizens’ actions on X, calling it a “fantastic initiative” and adding, “If [Prime Minister] Schoof and the VVD do not immediately deploy the army en masse for this, we will have to do it ourselves! I would like to participate next time!”

Wilders has been vocal about tightening the Dutch asylum regime. His party recently withdrew from the governing coalition after other parties refused to adopt his 10-point plan for what he called “the strictest asylum policy ever.” The cabinet’s collapse triggered early elections, which are scheduled to take place on Oct. 29, 2025.

Van Weel reiterated the government’s focus on “stricter asylum laws and better border control.”

Wilders, however, responded by accusing him of inaction. “Weakling. You don’t do anything at all. You could have had the army guard the borders now and sent away all asylum seekers on the basis of Article 72 TFEU, just like the Germans do,” he posted on social media. “If people are frustrated, it is because the VVD is completely failing.”

Ter Apel is the home of the Netherlands’ largest asylum reception center, where officially around 2,000 asylum seekers are currently housed.

In March, residents of Nieuw-Weerdinge, a Dutch town between Ter Apel and the nearest city of Emmen, launched a fundraiser in support of a 51-year-old local man convicted of assaulting an Algerian asylum seeker during an attempted citizen’s arrest.

He was found to have confronted an Algerian national from the reception center for allegedly stealing €40 from a delivery van.

The town has established its own neighborhood watch app used by concerned residents to ensure anyone acting suspiciously in the area is identified after a surge in crime.

https://www.zerohedge.com/geopolitical/well-do-it-ourselves-dutch-vigilantes-stop-cars-german-border-protest-over-illegal

Russia Launched Record Nearly 500 Drones In Overnight Attack On Ukraine

 In overnight attacks Russia launched a record 479 drones across Ukraine, with airstrikes reported in 10 locations, damaging buildings but surprisingly there were no immediate reports of deaths or mass casualties, with one person reported injured.

Ukrainian forces subsequently claimed to have intercepted 460 of the drones and 19 of 20 missiles. Western supplied anti-air defenses are still hard and work and remain effective in Ukraine, apparently.

Parts of a Shahed drone following an attack in Kharkiv on June 4, AFP

The mayor of Rivne called it the oblast's largest attack on a single night since the war began. Ukraine's President Volodymyr Zelensky acknowledged in a late Sunday statement that in some of those areas "the situation is very difficult."

Air raid sirens sounded for some ten hours in Kyiv oblast, local media reports, and further issued the following details:

According to the official statement, Russia launched 499 weapons, including 479 Shahed‑type attack drones and various decoy drones, four Kh‑47M2 "Kinzhal" air-launched ballistic missiles, 10 Kh‑101 cruise missiles, three Kh‑22 cruise missiles over the Black Sea, two Kh‑31P anti‑radar missiles, and one Kh‑35 cruise missile from occupied Crimea.

Ukraine had reportedly neutralized 479 of the incoming targets, with 292 were shot down, and 187 jammed or lost via electronic warfare.

On the other side, Ukraine also mounted a large-scale drone assault, again deep inside Russian territory, which resulted in direct hits and damage.

Ukraine forces said they struck a Russian electronics factory that produces drone components, causing a temporary shutdown.

Flames rise over the Russian city of Cheboksary in the Chuvashia Republic after drone strike on factory, Astra/Telegram

The VNIIR plant, one of the nation's largest producers of electronic components, is situated in southern Cheboksary, about 600 km east of Moscow and 1,000 km northeast of Ukraine’s border.

"This morning, Ukrainian attempts to use drones in Chuvashia were detected," regional head Oleg Nikolayev stated on Telegram, saying also "There were no victims from the attack" and that the situation is "entirely under control".

In all these latest factory strike, Kiev maintains it is hitting 'military targets' which are linked to the Russian army...

Yet it looks as if Ukraine struck yet another valuable target deep inside Russia, with questions remaining over the effectiveness for Russia's anti-air defense systems, which were designed to track and intercept larger inbound projectiles such as missiles.

* * * 

Below are more developing geopolitical headlines via Newsquawk:

• Russian forces captured Zoria in Ukraine’s Donetsk region and reached the Dnipropetrovsk region in Ukraine, according to TASS and Interfax. However, it was later reported that Ukrainian General Staff spokesman Kovalev denied claims by the Russian Defence Ministry that its forces advanced into Ukraine’s eastern Dnipropetrovsk region for the first time since it launched its full-scale invasion.
• Head of the Russian delegation at talks with Ukraine in Istanbul said Russia handed over to Ukraine the first list of 640 POWs for exchange, according to TASS. Furthermore, the Russian Defence Ministry said Russia launched a large-scale humanitarian operation to repatriate more than 6,000 bodies of deceased Ukrainian military personnel and exchange prisoners of war, while Ukrainian officials rejected Russian claims that Ukraine was delaying the exchange of soldiers’ bodies.
• Ukrainian drone attack sparked a short-lived fire at the Azot chemical plant in Russia’s Tula region, although there was no threat to air quality near the plant, according to the regional governor.
• US believes Russian retaliation for Ukraine’s drone attack is not over yet and it expects a multi-pronged strike.
• Poland scrambled aircraft to ensure airspace security after Russia launches strikes on Ukraine.

Another dramatic video out of Cheboksary:

https://www.zerohedge.com/geopolitical/russia-launched-record-nearly-500-drones-overnight-attack-ukraine

PolyPid Positive Topline Results from Phase 3

 

• D-PLEX100 successfully met the primary efficacy endpoint, with statistically significant results (p<0.005) in 798 patients with large abdominal surgery incisions.
• The trial successfully met all key secondary efficacy endpoints, including a 58% reduction in the rate of surgical site infections (“SSI”) in patients treated with D-PLEX100 arm versus standard of care (“SoC”) arm (p<0.005).
  
• The Company expects to submit a New Drug Application (“NDA”) to the U.S. Food and Drug Administration (“FDA”) in early 2026, with a Marketing Authorization Application (“MAA”) in the E.U. to follow shortly thereafter.
  
• PolyPid will conduct a conference call and webcast at 8:30 A.M. ET today.

Conference Call Dial-In & Webcast Information:

Date:	Monday, June 9, 2025
Time:	8:30 A.M. Eastern Time
Conference Call:	https://register-conf.media-server.com/register/BIb5bb85aa1ffc4940b78f7191b278ca77
Webcast:	https://edge.media-server.com/mmc/p/k6n5hrft

A replay of the presentation will be available on the Company’s Investor Relations Events and Presentations webpage following the event.

https://finviz.com/news/76248/polypid-announces-positive-topline-results-from-phase-3-shield-ii-trial-d-plex-demonstrated-significant-reduction-in-surgical-site-infections-and-successfully-met-primary-and-all-key-secondary-endpoints

IMAB at Jefferies

 On Thursday, 05 June 2025, IMAB (NASDAQ:IMAB) presented at the Jefferies Global Healthcare Conference 2025, revealing strategic insights into its clinical pipeline. The company highlighted both promising advancements and ongoing challenges, notably in its Claudin 18.2 bispecific antibody, Giva (FT825), aimed at addressing unmet needs in gastric cancer treatment.

Key Takeaways

• IMAB is financially robust with $168.8 million to support clinical developments.
• Giva (FT825) shows promise in frontline gastric cancer therapy, with an upcoming data release at ESMO GI on July 2nd.
• The company plans further data releases for Raji and Yuli in late 2025 and early 2026.
• IMAB’s team highlighted Giva’s unique features, including high binding affinity and reduced toxicity.

Financial Results

• IMAB holds $168.8 million, ensuring funding through key clinical readouts.
• The Claudin 18.2 positive gastric cancer market is valued at $12 billion, a target for Giva’s application.

Operational Updates

• IMAB employs 25 staff, focusing on clinical efficiency within the US.
• Giva’s dose expansion is progressing rapidly, with data to be presented at ESMO GI.
• Raji’s Phase I study aims to optimize dosing to minimize liver toxicity.
• Yuli’s Phase 2 study in lung cancer is underway, with results expected soon.

https://www.investing.com/news/transcripts/imab-at-jefferies-global-healthcare-conference-promising-pipeline-developments-93CH-4084099