Or­chard dis­creet­ly ax­es li­cense for 'bub­ble boy' gene ther­a­py, de­spite re­cent pos­i­tive long-term da­ta up­date

Less than a month af­ter pub­lish­ing pos­i­tive long-term da­ta for an ex­per­i­men­tal gene ther­a­py, Or­chard Ther­a­peu­tics has qui­et­ly ter­mi­nat­ed its li­cens­ing agree­ment over the pro­gram.

In an 8-K fil­ing to the SEC last Fri­day, Or­chard re­port­ed that it is end­ing the li­cense re­lat­ed to its OTL-101 can­di­date, in de­vel­op­ment to treat adeno­sine deam­i­nase se­vere com­bined im­mun­od­e­fi­cien­cy or ADA-SCID, known col­lo­qui­al­ly as “bub­ble boy syn­drome.” It’s a rare ge­net­ic dis­ease where pa­tients have al­most no im­mune sys­tem what­so­ev­er.

The move comes af­ter Or­chard pub­lished long-term re­sults in the New Eng­land Jour­nal of Med­i­cine show­ing all 50 pa­tients who re­ceived the treat­ment were still alive af­ter at least two years. Event-free sur­vival was al­so high, with 97% of US pa­tients and 95% of UK par­tic­i­pants not need­ing to re­turn to pri­or ther­a­pies.

Or­chard had been de­vel­op­ing the ther­a­py af­ter sign­ing the agree­ment with UCLA and Uni­ver­si­ty Col­lege Lon­don back in Feb­ru­ary 2016. The biotech has an­oth­er ther­a­py for ADA-SCID known as Strimvelis, ap­proved in Eu­rope in 2016, but halt­ed dos­ing af­ter a pa­tient treat­ed un­der com­pas­sion­ate use be­gan see­ing treat­ment for leukemia.

The idea be­hind OTL-101 is to use a lentivirus with hematopoi­et­ic stem cells, ad­min­is­tered ex vi­vo, to in­sert a func­tion­al copy of the ADA gene in­to pa­tients’ cells. Or­chard had been look­ing for an ap­proval for a while, hav­ing pre­vi­ous­ly won break­through ther­a­py des­ig­na­tion for OTL-101 from the FDA.

An FDA green­light had elud­ed Or­chard with the Covid-19 pan­dem­ic forc­ing them to push back plans to sub­mit a rolling ap­proval ap­pli­ca­tion. But last week’s SEC re­port may have been in the works for at least a year.

Back in May 2020, Or­chard an­nounced a new op­er­a­tional strat­e­gy in­volv­ing lay­ing off 25% of its staff and re­struc­tur­ing its pipeline to fo­cus less on rare dis­eases. Part of that re­struc­tur­ing, Or­chard said at the time, was to re­duce in­vest­ment in OTL-101 and an­oth­er pro­gram — steer­ing re­sources in­stead to­ward four oth­er can­di­dates clas­si­fied as “top near-term pri­or­i­ties.”

The pro­grams in­volved are be­ing set up to treat: metachro­mat­ic leukody­s­tro­phy (OTL-200), Wiskott-Aldrich syn­drome (OTL-103), Mu­copolysac­cha­ri­do­sis type I (OTL-203) and Mu­copolysac­cha­ri­do­sis type II­IA, al­so known as San­fil­ip­po syn­drome type A (OTL-201).

Or­chard went pub­lic in 2018, rid­ing a $200 mil­lion IPO af­ter two oth­er nine-fig­ure rounds with a $110 mil­lion Se­ries B and $150 mil­lion Se­ries B. The biotech worked with Glax­o­SmithK­line, too, ac­quir­ing the Big Phar­ma’s rare dis­ease unit — in­clud­ing Strimvelis — in ex­change for rough­ly 20% eq­ui­ty, al­so in 2018. The lack of an FDA-ap­proved prod­uct at this stage, how­ev­er, has left an­a­lysts with ques­tions.

So­cial im­age: Bob­by Gas­par, Or­chard Ther­a­peu­tics CEO

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.