Some of the world’s largest investors are taking a fresh look at an unloved Turkish bond market that could prove to be next year’s biggest bright spot in the $8 trillion local debt universe of developing nations.
Few are taking the plunge just yet, however, despite record-high yields on offer.
PE-style “whitelists” hamper efforts to expand the secondary market for fund stakes, as regulators raise liquidity concerns about private capital.
Attempts by some of private credit’s biggest names to develop a hot new corner of the $1.6 trillion market have hit a roadblock: their peers.
Buyers including Apollo Global Management, Ares Management and Tikehau Capital have raised billions to spend on so-called “secondary” deals, when an investor in a private credit fund decides to sell their stake early. But in some cases they’re being excluded from lists of approved acquirers by the firms who run the funds, according to people with knowledge of the matter.
With a confirmatory trial for Sarepta Therapeutics’ Duchenne muscular dystrophy trial ending in failure, Pfizer’s chief scientist says the pharma giant’s gene therapy is now “the main game in town.”
When asked about yesterday's DMD data drop from competitor Sarepta on Pfizer’s third quarter earnings call Oct. 31, CEO Albert Bourla said, “it is very, very bad news for patients,” noting that solutions are very limited for people with the severe genetic disease.
“This makes our gene therapy in a way the main game in town,” CSO and President of R&D Mikael Dolsten, M.D., Ph.D., said on the call.
Sarepta shared yesterday that its approved DMD gene therapy Elevidys failed to hit the primary goal of a pivotal study. The endpoint, a measure of motor function called the North Star Ambulatory Assessment, failed to reach statistical significance in the phase 3 study. Following the data reveal, the company's share price tumbled about 41% to $63.19 midday Tuesday.
When asked about progress on Pfizer’s own DMD program, a gene therapy currently being tested out in a phase 3 trial, Dolsten said there is an opportunity for an interim analysis by the end of this year, though he did not specify whether Pfizer would be taking that opportunity or not. The final analysis is expected by the second half of 2024, and Dolsten said he’s excited to “let the data tell the story.”
Dolsten said the candidate, known as PF-06939926 or fordadistrogene movaparvovec, has “shown a very consistent effect across biomarkers and functional endpoints.”
The data has also shown “encouraging signals in both the younger and the slightly older boys,” according to Dolsten, who added that those signals weren’t something seen in Sarepta’s data. Both Pfizer’s and Sarepta’s phase 3 studies have enrolled boys ages 4 to 7 years, with Sarepta’s Elevidys receiving accelerated approval in June to treat ambulatory patients ages 4 to 5 years.
Despite the new disappointing data, Sarepta still plans to file for a label expansion to treat "all DMD patients" and convert the accelerated approval into a traditional nod.
Two things could speed up Pfizer’s race to a potential FDA finish: fordadistrogene movaparvovec has nabbed both FDA fast-track and orphan designation. However, the therapy has had to face its own challenges, too.
In December 2021, the FDA placed a clinical hold on Pfizer’s phase 3 study after a patient death was reported in a phase 1 trial evaluating the asset. However, the program was freed from the hold the following spring after Pfizer implemented a protocol amendment and addressed the FDA’s requests regarding a potency assay.
Targeted IRAK4 protein degrader KT-413 did exactly what it was supposed to in an early-stage clinical trial, but Kymera Therapeutics is still jettisoning the program.
The Watertown, Massachusetts, biotech is cutting the lymphoma med for strategic reasons to focus resources on other areas of the pipeline, according to a Thursday third-quarter earnings release.
KT-413 had already shown target knockdown in the blood and tolerability in a phase 1 study. Kymera said the med achieved target degradation levels without spurring dose-limiting toxicities.
But, in this market, something has to go. The decision “reflects financial discipline around program prioritization,” said CEO Nello Mainolfi, Ph.D., in the release. The company will now be able to direct resources to therapies that have the potential to address larger patient populations with significant need and clear commercial opportunity.
“With the promise of our growing pipeline, and in the context of the changing diffuse large B-cell lymphoma treatment landscape, we have decided to discontinue the development of KT-413, despite the program having achieved desired target degradation levels without dose-limiting toxicities,” said Mainolfi.
The decision will extend Kymera’s cash runway into the first half of 2026, compared to a previous estimate of the second half of 2025. That should reach beyond key readouts for the biotech’s clinical programs. Kymera has $435 million in cash and equivalents as of Sept. 30.
With KT-413 cast off, Kymera will focus more on the Sanofi-partnered IRAK4 degrader KT-474/SAR444656. Sanofi just began dosing in a phase 2 study for hidradenitis suppurativa in October. The therapy is also being tested in atopic dermatitis. With the first patient receiving a dose, Kymera received a $40 million milestone payment.
Kymera will also showcase the lymphoma and solid tumor med KT-333 at the upcoming American Society of Hematology meeting. An abstract to be released today will detail a phase 1 clinical trial of 21 patients with 12 evaluable as of the data cutoff. Kymera said that one partial response had been achieved in a patient with cutaneous T-cell lymphoma (CTCL) after two treatment cycles, while three patients with solid tumors had stable disease after two cycles. The therapy was granted a fast-track designation in relapsed/refractory CTCL and relapsed/refractory peripheral T-cell lymphoma.
Enrollment has also been completed in a phase 1 study of KT-253 for solid tumors and lymphomas.
Kymera will hold a virtual R&D day on Jan. 4, 2024.
https://www.fiercebiotech.com/biotech/kymera-cuts-lymphoma-med-performed-expected-phase-1
A critical tenet of Moderna’s business so far has been having sole rights over virtually every clinical-stage asset in the pipeline. That soon may change depending on sales moving forward.
“If we have to, we will be open, of course, to partnerships [for] some of those programs,” CEO Stéphane Bancel told analysts on a third-quarter earnings call. Any fervor to out-license some programs is contingent on how sales look, explained Bancel, who didn't expand on which programs are most likely to be up for grabs.
Moderna projected $4 billion in sales in 2024 and a “return to growth” in 2025 as part of its earnings presentation. The CEO's comments on partnerships followed a question about how much flexibility the company will have in adjusting R&D and SG&A spending in 2025, which the company guided as being flat to down, “with ability to flex.” Bancel said partnership considerations were incorporated into the R&D spending guidance.
The collaboration considerations come as Moderna is dealing with the same COVID vaccine sales crunch that’s hit fellow manufacturers like Pfizer and BioNTech. The company had to write off $1.3 billion in excess or obsolete products and reframed its guidance to project “at least” $6 billion in vaccine sales, assuming 50 million doses in the U.S. market. It’s a notable change from the $6-8 billion projection maintained for much of the year.
Only a few weeks ago, Bancel was more bullish on sales. “Do I really [think it's] going to be as low as 50 [million doses]? I don't," he told Fierce Pharma in an interview back in September.
Moderna is also slashing manufacturing costs, which in the short term will translate to $1.6 billion in charges through the end of the year. CFO Jamey Mock committed to completing facilities in the U.K., Canada and Australia, but that no more capacity was needed for respiratory-related production.
More than a decade after AstraZeneca appeared to give up hope of using zibotentan to treat prostate cancer, the endothelin receptor antagonist has received a new lease on life as a combo treatment for chronic kidney disease (CKD) patients.
A combo treatment of 1.5 mg zibotentan and 10 mg of the Big Pharma’s blockbuster CKD and diabetes drug Farxiga was shown to induce a 52% mean reduction in albumin-to-creatinine ratio (UACR)—an indicator of albuminuria—compared to baseline after 12 weeks of treatment.
A combo with a lower, 0.25-mg dose of zibotentan resulted in a similar 47.7% reduction in UACR, AstraZeneca demonstrated in data from a 447-patient phase 2b study presented at the American Society of Nephrology Kidney Week.
When compared to Farxiga alone, the high-dose combo saw a 33.7% greater reduction in UACR, with the lower dose seeing a 27% greater reduction.
High proteinuria—a high level of protein in urine—affects around 10% of patients with CKD and is associated with a higher risk of heart attack and kidney failure, AstraZeneca noted in its Nov. 3 release.
Zibotentan works by improving kidney blood flow and reducing albuminuria and vascular stiffness. However, one issue with endothelin A receptor antagonists that has been identified in other clinical trials has been high rates of fluid retention. While the high-dose cohort in the zibotentan/Farxiga trial also saw an 18.4% rate of these events, the low-dose cohort saw a lower rate of 8.8%, close to the 7.9% rate among the Farxiga monotherapy cohort, AstraZeneca noted.
Today’s results suggest that AstraZeneca’s persistence with zibotentan has paid off after the drug suffered a pair of late-stage trial failures in prostate cancer in 2010 and 2011. Now, the company plans to kick off a phase 3 trial of the combo treatment in CKD before the end of the year.
“The evidence published today supports advancement of zibotentan/dapagliflozin into a phase 3 clinical trial to further assess its potential as a first-in-class treatment for residual proteinuria in CKD,” Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, said in the release.
“Elevated levels of albuminuria are associated with an increased risk of kidney function loss over time and by reducing the level, we can lower the risk of progression to kidney failure,” Hiddo Heerspink, Ph.D., of the department of clinical pharmacy and pharmacology at the Netherlands’ University of Groningen added in the same release.
A leading Republican senator Sunday slammed the Biden administration for “having its head completely buried in the sand” over the US border crisis — and creating a “massive national security issue” as a result.
“One-point-seven million ‘gotaways.’ We don’t know who these people are,” Republican Sen. Ron Johnson of Wisconsin told host John Catsimatidis on the “Cat’s Roundtable” on WABC 770 AM radio, referring to the reported number of illegal migrants who have streamed across the US southern border and evaded apprehension since President Biden took office in 2021.
“We just know that we detect them coming across the border and now they’re in our country,” Johnson said.
“You think there might the a terrorist or two in that 1.7 million people?” he asked. “This is a massive national security threat that President Biden is completely turning a blind eye toward.
“This administration has its head completely buried in the sand,” Johnson added. “They won’t even admit it’s a problem, John. They call it a challenge.”
Johnson also targeted Homeland Security Secretary Alejandro Mayorkas, calling his testimony before Congress last week “maddening.
“I asked him point-blank, ‘Mr. Secretary, how many people have you let in during your administration?’ ” Johnson said. “He just hemmed and hawed. He never answered the question at all. This is a guy who completely blames the explosion on the border on our broken asylum system.
“I had to point out to him, ‘Mr. Secretary, under Donald Trump, the exact same broken asylum system, we pretty well secured the border. We, in one month, had only 17,000 people coming into this country illegally,” he said. “Last month, we had over 270,00.”
The senior senator also lambasted FBI Director Christopher Wray, saying Wray “utterly failed” to “restore the credibility and integrity of the FBI” and accusing him of attempting to derail the corruption probe into troubled first son Hunter Biden.
He accused Wray and other federal agencies of trying “to throw us off the trail.
“This is corruption at some of the highest levels of the FBI,” Johnson said. “We know how corrupt the investigation has been of Hunter Biden — the Department of Justice frustrating investigators’ ability, the IRS, the whistleblowers who’ve talked about this.
“As troubling as the corruption of the Biden crime family is, what may be even more troubling is the corruption within federal law enforcement, the FBI, Department of Justice, [the] intelligence community.”
