Orchard Therapeutics

Fierce 15

Ambition to be the first gene therapy product approved in the U.S.

CEO: Seeking permanent chief executive; currently managed by F-Prime Capital team
Based: Los Angeles, CA
Founded: 2016
Clinical focus: Rare and ultrarare genetic diseases

The scoop: Orchard is seeking to rival GlaxoSmithKline ($GSK), using some of its former employees, to create a better, more effective and potentially safer version of the recently approved “bubble boy syndrome” med Strimvelis, using the latest, cutting-edge tech in a patient population that has fewer than 100 patients worldwide.

What makes Orchard Fierce: Orchard’s development programs are focused on ex vivo autologous hematopoietic stem cell gene therapy designed to restore normal gene function in primary immune deficiencies, metabolic diseases and hematological disorders.

This pioneering tech uses a sample of the patient’s own stem cells, which are modified with a functioning copy of the missing or faulty gene before being transplanted back into the patient’s body. Using the patient’s own cells (autologous) removes the need to search for a matching stem cell donor, which can take months or even years.

The small biotech’s early candidate is an ex vivo autologous lentiviral stem cell gene therapy for severe combined immunodeficiency (SCID), also known as bubble boy syndrome, as children with the disorder are so susceptible to infection they have to be constantly protected and must live in a sterile environment. Orchard is also exploring the effects of ex vivo autologous lentiviral stem cell gene therapy in patients with mucopolysaccharidosis type IIIA (MPS IIIA, or Sanfilippo disease type A).

Only about 15 patients in Europe have ADA-SCID, but this year the EU approved the first gene therapy for the disease, GlaxoSmithKline's Strimvelis (autologous CD34+ cells transduced to express ADA). Patients must however travel to Ospedale San Raffaele in Milan, Italy, as this is currently the only place where the drug can be manufactured and given to a patient.

If there is already a drug for the condition, and for a condition that only affects a handful of patients, why is Orchard bothering to create its own version? Ben Auspitz and Alexander Pasteur told FierceBiotech that their therapy can become unrivaled in efficacy and safety in this field.

“We have brought together from across the world the who’s who of gene therapy,” Auspitz explained. Orchard’s founding scientists include professors Adrian Thrasher and Waseem Qasim from UCL and GOSH, who have been pioneering ex vivo autologous hematopoietic stem cell gene therapy for the last 20 years.

They also recently bagged two major names from GSK who were working on Strimvelis: namely, Andrea Spezzi, CMO, and Nicolas Koebel, SVP of business operations, who prior to joining Orchard were involved in the clinical development and market access planning at GSK.

Koebel was at GSK for 10 years, until 2015. In 2011, he was appointed global commercial lead to GSK's Rare Diseases Unit, to oversee the commercialization of GSK's program of autologous ex vivo gene therapies.

Spezzi, meanwhile, served as VP and medicine development leader at GSK's Rare Diseases Unit, after working for Takeda as its global medical director for R&D. 

“We have the best in class team combined with the best in class science, so we are set up to deliver tremendous medicines,” Auspitz says.

They are still keeping some data close to their chests, with results expected to be made public in the coming months, but Auspitz said that “over 30 patients with ADA-SCID have been treated with our therapy, and we had a 100% survival rate. These results are astonishingly good.”

But why is their lentiviral treatment better than what GSK is offering? Pasteur said: “The core difference is that GSK’s tech is based on a gamma retrovirus, which is old, outdated, 1970s and 1980s technology. This was pioneering at the time, but now superseded by lentivirus. This has an uncontroversial and uncontested safety benefit over gamma retrovirus, and so we believe we have the safest vector out of our therapy and GSK’s.

“There have been some serious safety issues and tragedies in the 1980s with the first-gen technologies whereby it actually induced leukemia. The whole rationale behind lentiviral is to get away from this. To be fair to GSK, they have treated 18 patients and they’ve had zero cases of leukemia, so their product looks good so far. But, there is this sword of Damocles that is hanging down over the field, which we want to remove with our product. We also believe we have better efficacy, but the data for that will be revealed a little further down the line.”

There is also the issue of manufacture. Pasteur explained: “Strimvelis has been approved to be made at just one site: in Milan, Italy, so patients and their families have to travel to Milan for around three months. This is a significant burden on the family to have to travel from anywhere in Europe to Milan to be treated. And of course you have the referral politics where many doctors aren’t keen on sending their patients off to a foreign land.”

GSK has told FierceBiotech that it intends to locate more centers around Europe with a freezing process for Strimvelis so it can be moved, but this is likely a few years down the line.

“So, a Milanese-only site is a severe limitation of Strimvelis,” Pasteur says. “The Orchard product, while I can’t go into too much detail now, will not have such restrictions in terms of where it has to be used. It will be provided in a form which means it can be used at multiple sites. We think that’s a huge advantage.

“So overall, we think we have a better working, safer and easier to use product with a world-leading team of gene therapy pioneers and will capture a major part of the ADA-SCID market, despite it being so small and with Strimvelis already approved.”

Both Pasteur and Auspitz believe they can also see their treatment become the first of its kind approved in the U.S. Only time will tell, but their ambitions are huge.

Investors: F-Prime Capital, with support from UCL Business and additional participation from the UCL Technology Fund

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Orchard Therapeutics