Skyhawk's Early Huntington Signal Faces a Bigger Test & Sling Raises $123M

Skyhawk's Huntington's drug has an encouraging fifteen-month signal. But the comparison comes from historical patients, and just fifteen treated people were evaluable. That changes how much confidence the result can carry.

Sling has raised a hundred and twenty-three million dollars for an oral thyroid eye disease drug. And Novartis exercised a brain-delivery option worth another look. Let's get into it.

Welcome to The Pharma Closeout for Wednesday, September sixteenth. I'm Alex Mercer.

I'm Maya Patel. We'll get you caught up on what changed today, with enough context to make sense of the headlines.

Our top story is Skyhawk's experimental oral drug, SKY-0515. The company released final fifteen-month results yesterday from its Phase one-two Huntington's study. Huntington's is an inherited disease that damages the brain. This study follows movement, thinking and everyday function. The attraction is a daily pill aimed at changing the course of the disease, beyond medicines that manage individual symptoms.

Skyhawk measured those abilities on a composite scale, where higher scores are better. At fifteen months, the fifteen evaluable treated people improved on average, while an externally assembled natural-history group's average declined. The reported difference was one point five nine on that scale. That's a group result, not evidence that every patient improved.

A clinical measure is more useful than a laboratory result alone. But these weren't patients who stayed on placebo alongside the treated group for fifteen months. What can we take from that comparison?

A reason to test the signal more rigorously. Randomization lasted twelve weeks; everyone received active treatment in the extension. The longer-term comparison uses historical patients, weighted to make the groups more comparable. That helps, but differences between the groups could still account for some of the result. And we can't translate a change on this combined score into a particular activity someone regained.

Let's put the competitive context around it. Novartis already has its oral Huntington's drug, votoplam, in Phase three. Skyhawk would be competing for a role in slowing progression, not arriving in an empty field. A daily pill is an appealing proposition, but that route alone won't distinguish it from another oral program. The clinical evidence has to carry the case.

And the larger placebo-controlled FALCON-HD trials are where Skyhawk can test that case with treated and untreated patients followed together. Safety matters alongside any functional benefit. Skyhawk reports no treatment-related serious adverse events through fifteen months in this early study. The larger studies will give us a broader basis for judging both.

Skyhawk has a result worth following in that race. Whether the separation survives a concurrent placebo comparison is the question that could change its competitive position.

In the deal roundup, Novartis exercised its Sironax option, with a hundred and twenty-five million dollars due after closing. Novartis gets full global rights to the brain-delivery platform. The original option agreement dates to last year; today's development is the exercise. Sironax keeps rights to develop selected assets using the platform.

This is a preclinical delivery bet: helping large therapeutic molecules cross the blood-brain barrier. A drug aimed at a brain disease still has to reach the place it needs to work. Novartis is taking control of the platform, while Sironax retains a way to develop some assets itself. The rights split leaves both companies with a role in its development.

Separately, Saol Therapeutics disclosed up to a hundred and fifteen million dollars in milestone-linked capital from Oaktree. The transaction closed September eleventh. An initial tranche supports launch preparation, with the rest dependent on milestones. That distinction matters: the full headline amount isn't unconditional funding.

The program is SL1009, sodium dichloroacetate, for pyruvate dehydrogenase complex deficiency, a rare mitochondrial disease. Its resubmitted application has a December thirtieth FDA target date. Saol is funding preparation for a possible launch while that review runs. The capital is arriving ahead of the regulatory decision, when the company still has an uncertain outcome to plan around.

One more pipeline move: IASO says FDA cleared its application to test IASO208 in the United States. The planned Phase one-b study is in adults with relapsed or refractory B-cell non-Hodgkin lymphoma. This is an in-vivo CAR-T approach: a viral vector carries instructions intended to generate cancer-targeting T cells inside the patient.

That changes where the cell-engineering work happens. Instead of taking a patient's cells out to manufacture the treatment, the approach aims to do that work in the body. The US clearance allows that proposition to move into testing. Patient evidence will have to show whether the different delivery method can produce useful, manageable treatment.

In Regulatory Watch, Cogent now has a third bezuclastinib filing under FDA review. The latest acceptance is for advanced systemic mastocytosis, a disease involving uncontrolled mast-cell growth. The target action date is June twenty-ninth, twenty twenty-seven. Bezuclastinib is designed to inhibit disease-driving KIT mutations, and this filing draws on the previously reported APEX trial.

The order of those decisions is useful context. The gastrointestinal stromal tumor application comes first, with a November thirtieth target this year. Nonadvanced systemic mastocytosis follows in December. Those two nearer-term decisions come before this newly accepted advanced-disease filing. One asset, three patient populations, and three separate reviews.

Each review has its own evidence and proposed use. A decision in one population won't settle the others. For the advanced-disease application, the APEX results were already presented earlier this year. What changed is that FDA accepted the filing and set the June target, giving this part of the program a defined review timetable.

FDA also published a broader look at first-cycle complete responses: applications that finished an initial review without being approved as submitted. Its analysis follows submissions received in fiscal years two thousand eight through twenty twenty-four. That matters because it follows application cohorts, rather than counting whichever approval or setback headlines appeared in a particular year.

And the broad finding challenges a simple narrative that first-review setbacks have been steadily getting worse. But the report doesn't establish steady improvement either. One statistical approach suggests a long-run decline; another doesn't confirm a consistent trend. An earlier downward shift, followed by fluctuations, may explain more of the pattern.

That's the limit to keep with it. The report excludes the twenty twenty-five cohort because too many applications were still awaiting decisions. It cannot tell us what recent policy or leadership changes have done. And a complete response is a setback in a review, not necessarily the end of a medicine's path: applications can be resubmitted and later approved.

At the manufacturing-site level, FDA posted a warning letter to Bausch and Lomb's Tampa facility. The letter is dated September fourth, following a March inspection. FDA describes repeated weaknesses in sterile-production controls, including environmental monitoring and aseptic practices, and calls for independent assessments and corrective action.

The concern is the system intended to keep products sterile, rather than one isolated paperwork problem. A warning at that level can matter to the people responsible for quality and reliable supply. But we don't have a demonstrated supply interruption here, and the letter itself is not a recall or a shutdown. The required corrections are the concrete next step.

On access, Gilead and the Pan American Health Organization announced a regional procurement pathway for twice-yearly lenacapavir to prevent HIV. The agreement uses PAHO's Regional Revolving Funds to support country-led adoption across Latin America and the Caribbean. It adds a route for fourteen countries outside Gilead's voluntary licensing agreements.

Those countries need a different route from the generic access arrangements already in place elsewhere. This agreement helps create one. It doesn't mean doses are already reaching everyone who could benefit. Price and rollout timing were not disclosed, and each country's implementation still matters.

Gilead and PAHO have created a procurement mechanism for a long-acting prevention option, with the practical terms of delivery still to come. That's a meaningful step between having a medicine and making it available across different health systems.

Quick note before our second top story today — if The Pharma Closeout is how you close out your day, follow the show on Spotify or Apple Podcasts.

Our second top story is Sling Therapeutics and its hundred-and-twenty-three-million-dollar Series C. The private biotech is advancing linsitinib, an experimental oral drug for thyroid eye disease. Sling also announced that the first patients have already been dosed in ORBIT, its Phase three trial.

Thyroid eye disease is an autoimmune condition that can cause swelling and bulging around the eyes, pain, and, in severe cases, vision loss. Linsitinib targets IGF-1R, the same pathway addressed by the approved infused antibodies Tepezza and Lumvoa. Its potential distinction is a pill taken twice a day. The target is already used in treatment; the oral approach is what makes this program different.

There's a commercial opening for a pill in a field served by infusions. That gives Sling a clear proposition to develop, even with established treatments already available. What does ORBIT need to show before that route difference becomes a credible treatment choice?

It needs to confirm a treatment effect against placebo. ORBIT plans about a hundred and thirty adults with active, moderate-to-severe disease, taking linsitinib or placebo twice daily. The key assessment comes at twenty-four weeks and measures improvement in eye protrusion. Sling's earlier LIDS study met its primary endpoint, according to the company's topline report. Reproducing that finding in another controlled study is the job here.

The hundred and twenty-three million dollars funds that next stage of development. An oral route gives Sling a way to stand apart; convincing results would give the proposition substance.

And ORBIT compares the pill with placebo, not with Tepezza or Lumvoa. It can strengthen the evidence that linsitinib works without establishing better efficacy or safety than either infusion. Those are different questions, even if both matter to its eventual place in treatment.

Looking ahead, Skyhawk and Sling have distinct tests: whether the Huntington's signal holds against concurrent placebo, and whether the oral thyroid eye disease result repeats. For Gilead's lenacapavir access agreement, the next useful details are price and country rollout.

On the regulatory calendar, Cogent's GIST target comes first in November. Its nonadvanced mastocytosis application and Saol's resubmission have December targets. Those are dates for FDA action, while the clinical programs we've discussed still have studies to complete.

Skyhawk's small study gives us a reason to watch its larger trials closely. Sling has new capital behind its next one. Both stories are worth carrying forward, with a clear question attached: will the next controlled results support the treatment people are hoping for?

Thanks for spending part of your evening with us. I hope the rest of your Wednesday gives you a little room to enjoy it. Take care.

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