Gene Therapy, Results

Solid Bio is hit by another setback as initial biopsies spotlight a flop for Duchenne MD

Solid Biosciences has had another setback.

The biotech announced this morning that its dose-ascending Phase I/II study of its lead gene therapy for Duchenne muscular dystrophy flopped, sending the company into overdrive to hustle a higher dose into the clinic.

Ilan Ganot

The company announced Thursday morning that a 3-month biopsy of a handful of patients “showed low levels of microdystrophin protein expression.” In 2 of 3 patients, protein expression was undetectable by western blot analysis. In the third patient the dystrophin expression hit only 5% by western blot analysis, while analysts and the company were looking for 10% or better.

The company’s shares imploded, plunging 68% by the close. Shares of Sarepta, which has the only custom therapy on the market, jumped about 7% and then slid into the red.

Given the safety issues that the therapy has already run into, Leerink’s Joseph Schwartz questioned the company’s ability to power up an effective dose without threatening patients.

Our thesis that investors should focus not only on the quantity of microdystrophin expression but also on the quality of the expressed protein appears to be at significant risk based upon the increasingly uncertain ability of SGT-001 (Duchenne muscular dystrophy/DMD) to be safely dose-escalated to a level which is sufficient to achieve competitive microdystrophin levels. We believe it is prudent to wait and see if SLDB can achieve adequate levels of expression in a safe manner before considering whether the microdystrophin protein that is expressed by SGT-001 is differentiated from that of SRPT and PFE (Bamboo).

CEO Ilan Ganot quickly spotlighted the company’s cash reserves, a common strategy for distressed companies.

He noted: “This strategy is further supported by our scalable manufacturing process, from which we have sufficient drug product available to dose escalate without delay. We have the financial resources to execute on our plan and look forward to communicating additional data later this year.”

Ganot — a former JP Morgan investment banker — has made much of the fact that he’s a Duchenne MD dad out to find a gene therapy that could cure the lethal, rare disease. By introducing a synthetic dystrophin transgene construct, called microdystrophin, via a viral vector, the company has encouraged hopes it can do what Sarepta and others have been groping for with one decisive intervention. And he had attracted some heavyweight backers, including RA Capital and their colleagues at Bain.

The company ran into early trouble, though.

The very first patient to be treated with SGT-001 experienced a serious adverse event, triggering alarm bells after investigators saw a “decrease in platelet count followed by a reduction in red blood cell count, transient renal impairment and evidence of complement activation.” That triggered a clinical hold that lasted several months.

It wasn’t the first brush with trouble.

In the lead up to its IPO Ganot neglected to tell investors about an initial clinical hold on the program, posting that news just ahead of the listing. The biotech was also forced to note that gene therapy pioneer James Wilson from Penn had resigned from their scientific advisory board due to rising safety concerns related to high dosing using the vector he had developed.


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Head of Business Development
Wren Therapeutics Boston, MA
Life Sciences Venture Professional
Northpond Ventures Washington, DC
Senior Drug Discovery Oncologist
Schrödinger New York, NY

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