In late November, Soleno Therapeutics (Nasdaq: SLNO) announced that FDA had pushed the PDUFA date for their DCCR / Prader-Willi Syndrome NDA by three months, from December 27th to March 27th. According to the company, the FDA extended the PDUFA to review recently received information without citing any specific efficacy, safety, or manufacturing concerns. Although disappointing, many investors and analysts view a PDUFA push as a sign that FDA is leaning towards approval (why not simply CRL otherwise?). However, the recent CRL received by Applied Therapeutics (Nasdaq: APLT) has caused some concern amongst Soleno investors over whether they are misinterpreting FDA’s body language around the PDUFA push.
Relevant Parallels?
Without getting into too many details, there are some parallels to the Applied and Soleno stories. Applied’s NDA was for a rare pediatric disease; they were expected to have an Advisory Committee (Adcom), but it never developed, and they had their PDUFA pushed three months. To be clear, Applied’s NDA was for a different drug, indication, and FDA division, but investors still saw parallels, particularly with FDA’s oscillation around an Adcom and the PDUFA push. A more tenuous parallel was drawn between the companies’ pivotal data. Applied missed the primary endpoint in their pivotal Phase 3 study, as did Soleno in their initial Phase 3. However, unlike Applied, which submitted an NDA based on “statistical trends” and secondary endpoint data from Phase 3, Soleno ran a subsequent randomized withdrawal study (RWS) that met its primary endpoint. Still, for those looking for parallels, one could argue that neither company took a conventional NDA path (if that even exists in pediatric rare diseases).
FDA’s Body Language
We have consistently said in our writing on Soleno that an Adcom would be great biotech theater and likely helpful for DCCR’s probability of approval. As one of our favorite biotech social media voices (@Sports_bios) wrote recently when discussing the parallels between Soleno and Applied, “…in controversial data cases in orphans, fear NOT an adcom – fear MORE when you don’t know what you are walking into…” The PDUFA push opens a window for the FDA to revisit an Adcom, which we think could be a de-risking event for Soleno. However, in his recent Piper Sandler webcast, Soleno’s Anish Bhatnagar reiterated that based on the company’s most recent FDA interaction, the agency had not asked them to prepare for an Adcom.
Without an Adcom, investors are left trying to interpret FDA’s body language around the PDUFA push and whether the parallels with Applied are relevant. As @Sports-bio wrote, without an Adcom, the company and investors are left wondering “what they are walking into” as the March PDUFA draws closer.
Muscling Into the DMD Discussion
Earlier this week, Satellos Biosciences (US: MSCLF, TSX: MSCL) announced a $40mm financing to support their ambitious clinical plans for their lead asset, SAT-3247, in Duchenne muscular dystrophy (DMD). The company is currently enrolling the multi-ascending dose (MAD) cohort of their Phase 1 study and, in parallel, has begun dosing a small ten-patient adult DMD cohort. In 2025, Satellos plans to enroll multiple Phase 2 DMD studies across different age groups, including open-label and randomized controlled studies. There should be a steady cadence of data from these studies next year, starting with the MAD cohort in 1Q2025, then the adult DMD cohort in 2Q2025, and likely Phase 2 open-label data in 2H2025.
***Satellos November 2024 Corporate Deck
Ambitious Plans
We first wrote about Satellos in September 2023, stating, “Satellos is taking an entirely novel approach to the treatment of Duchenne by focusing on stimulating muscle regeneration as opposed to slowing muscle degeneration. While Sarepta and others focus on muscle fiber and dystrophin production, Satellos targets muscle stem cells and reinstates their ability to produce new muscle.” The differentiated mechanism of action of SAT-3247, an oral small molecule AAK1 inhibitor, allows Satellos to take a very broad approach toward its development. The company believes SAT-3247 could be beneficial in ambulatory and non-ambulatory patients. They also believe SAT-3247 can be used alongside other common DMD treatments and, therefore, plan to include patients who have received gene therapy, exon-skippers, and steroids in their studies. That’s why we refer to Satellos’ clinical plans for SAT-3247 as ambitious. Satellos will arguably study SAT-3247 in the broadest and most diverse population of any DMD-focused company.
Charting a New Course
Although Satellos is focused on safety and PK for the adult DMD cohort, investors will undoubtedly be interested in any hints of efficacy when these data are reported in 2Q2025. Unlike gene therapy or exon skippers, dystrophin expression, the surrogate endpoint Sarepta Therapeutics (Nasdaq: SRPT) has leveraged for several FDA approvals isn’t a relevant endpoint for SAT-3247. That’s because SAT-3247 works independently of dystrophin by targeting muscle stem cells.
Satellos will test for several standard biomarkers used in early-stage DMD studies. One such biomarker is creatine kinase (CK), a protein associated with muscle damage commonly measured in early muscular dystrophy studies. Satellos reported trends toward lower CK levels with SAT-3247 earlier this year in their canine data. Although considered a good screening marker in early disease, it is considered less predictive of disease progression and drug activity, especially in older patients with little remaining muscle.
***Satellos 29th Annual Congress of the World Muscle Society Poster
On its recent webcasts, the company has also emphasized regenerative index (RI) as an endpoint that reflects SAT-3247’s ability to improve muscle architecture, even suggesting the possibility of it becoming a surrogate endpoint for FDA approval. However, muscle biopsies are required to measure RI. Given the poor muscle composition of these later-stage patients in the ongoing adult DMD cohort, the company is not planning on taking biopsies. Nonetheless, the company will take muscle biopsies from an open-label adolescent cohort that it plans to initiate in the spring, raising the possibility of RI data as early as 2H2025.
Investors will also look for hints of functional benefits from the adult DMD cohort. These DMD men will all be non-ambulatory, so functional measures will likely be limited to the upper limb (pull and grip), pulmonary, and cardiac tests. A functional signal would be surprising, albeit highly encouraging, in a small sample size of later-stage patients over a 28-day course of therapy. Then again, the company’s Chief Medical Advisor, Dr. Jordan Dubow, said on a recent PropThink-hosted webinar when discussing the adult DMD cohort, “...we’re obviously going to look to ensure that the PK profile in the (DMD) patient population would look very similar to the healthy volunteers. Then, also looking for early signs of efficacy…we think there is a chance we may start seeing some functional benefits in these adults.” Regardless, Satellos is moving quickly with its ambitious clinical plans, and investors will not have to wait long before seeing data on SAT-3247 in DMD patients.
Sinking Fast
The calamity that is Cellectar Biosciences (Nasdaq: CLRB) may be coming to a merciful end. Last week, the company announced that FDA was now requiring a confirmatory study for CLR 131 in Waldenstrom’s macroglobulinemia (WM) before accepting an NDA for review. This is a reversal from the guidance the company gave investors less than a month ago on their Q3 call when they claimed they only needed alignment with FDA on the design of the confirmatory study before they could submit an NDA for accelerated approval. As opposed to the six-month NDA submission delay they had guided on their Q3 call, last week’s announcement would result in a multi-year delay and cost $10s of millions, money the company doesn’t have and likely cannot access. Perhaps its legacy shareholders throw it a life preserver, but it looks like Cellectar is sunk at this stage.