Sarep­ta posts ear­ly, rosy gene ther­a­py da­ta for limb gir­dle mus­cu­lar dy­s­tro­phy — fu­el­ing $165M buy­out of part­ner

Sarep­ta Ther­a­peu­tics $SRPT has re­vealed a promis­ing, ear­ly snap­shot of re­sults for its sec­ond gene ther­a­py pro­gram in pa­tients with a pro­gres­sive mus­cle de­gen­er­a­tive dis­or­der — months af­ter re­port­ing en­cour­ag­ing da­ta for its Duchenne gene ther­a­py, as the com­pa­ny for­ti­fies its sta­tus as a bonafide gene ther­a­py play­er. And the re­sults in­spired a $165 mil­lion buy­out.

Doug In­gram

On Wednes­day, Sarep­ta di­vulged da­ta from three pa­tients in the first co­hort of an open-la­bel Phase I/II study test­ing the use of an ex­per­i­men­tal gene ther­a­py — MYO-101 — in limb gir­dle mus­cu­lar dy­s­tro­phy (LGMD), a group of rare pro­gres­sive ge­net­ic dis­or­ders char­ac­ter­ized by wast­ing and weak­ness of the vol­un­tary mus­cles of the hip and shoul­der ar­eas (limb-gir­dle area) that have no ap­proved treat­ments.

The ther­a­py — which in­fus­es the cor­rec­tive gene us­ing a virus as a ve­hi­cle — is de­signed to treat LGMD2E, al­so known as be­ta-sarco­gly­canopa­thy, a se­vere form of LGMD char­ac­ter­ized by pro­gres­sive mus­cle fiber loss, in­flam­ma­tion and mus­cle fiber re­place­ment with fat and fi­brot­ic tis­sue.

MYO-101, along with four oth­er ex­per­i­men­tal LGMD gene ther­a­pies, was in-li­censed for $60 mil­lion by Sarep­ta last May from a pri­vate biotech called My­onexus (which burst on­to the scene with $2.5 mil­lion in seed fund­ing in 2017). On Wednes­day, Sarep­ta said it had ex­er­cised its op­tion to buy the com­pa­ny for $165 mil­lion.

Tri­al da­ta on the three pa­tients showed the ther­a­py re­ju­ve­nat­ed the pro­duc­tion, by an av­er­age of 51%, of be­ta-sarco­gly­can, the pro­tein re­quired for mus­cle func­tion that is miss­ing in this pa­tient pop­u­la­tion. The da­ta were mea­sured fol­low­ing a mus­cle biop­sy 60 days fol­low­ing in­fu­sion.

Whether the en­hanced pro­duc­tion of the be­ta-sarco­gly­can trans­lates to func­tion­al im­prove­ments re­mains to be seen, and the com­pa­ny will pro­vide those da­ta as it an­a­lyzes them at an up­com­ing med­ical meet­ing.

Cred­it Su­isse’s Mar­tin Auster pre­dict­ed that the ev­i­dence of po­ten­tial func­tion­al im­prove­ments ver­sus nat­ur­al his­to­ry da­ta would be made at the MDA con­fer­ence sched­uled for April 13 to 17.

How­ev­er, based on pre­clin­i­cal da­ta, Sarep­ta said that func­tion­al im­prove­ments are seen with more than a 20% im­prove­ment in be­ta-sarco­gly­can pro­duc­tion.

In the tri­al, one of the sec­ondary end­points was the re­duc­tion in cre­a­tine ki­nase (CK), an en­zyme found in the blood that is typ­i­cal­ly el­e­vat­ed as a re­sult of mus­cle dam­age. Ini­tial da­ta showed that MYO-101 dra­mat­i­cal­ly re­duced CK lev­els on av­er­age by 90%, Sarep­ta said.

“We think every mea­sure of ef­fect ex­ceeds ex­pec­ta­tions and like­ly puts this pro­gram on a fast track to ap­proval,” Baird’s Bri­an Sko­r­ney wrote in a note.

Un­like Duchenne pa­tients, those af­flict­ed with LGMD are typ­i­cal­ly not treat­ed with steroids as stan­dard, back­ground ther­a­py. In this tri­al, pa­tients were start­ed on steroids be­fore they were in­fused with the gene ther­a­py.

Two pa­tients were fol­lowed up af­ter 90 days had el­e­vat­ed liv­er en­zymes — an is­sue that has cropped up in oth­er gene ther­a­py tri­als such as AveX­is’ (No­var­tis) SMA pro­gram — with one deemed as a se­ri­ous ad­verse event. How­ev­er, Sarep­ta said the lofty liv­er sig­nal oc­curred when the pa­tients were ta­pered off oral steroids, and symp­toms re­solved up­on sup­ple­men­tal steroid treat­ment.

The co­hort da­ta, al­though ear­ly, have a po­ten­tial read-through to all the limb-gir­dle pro­grams, Sarep­ta CEO Doug In­gram said on a con­fer­ence call with an­a­lysts on Wednes­day. The com­pa­ny’s shares $SRPT jumped about 8% in ear­ly trad­ing.

The promise of gene ther­a­pies is in­tox­i­cat­ing as they are po­ten­tial one-shot cures for pre­vi­ous­ly un­touch­able dis­eases. In just a lit­tle over a year now, SanofiNo­var­tis and Roche have all in­vest­ed in with multi­bil­lion-dol­lar gene ther­a­py M&A deals, snap­ping up the pi­o­neers in the field. Ear­li­er this week, Roche mag­ni­fied the en­thu­si­asm with its $4.3 bil­lion bet on Spark Ther­a­peu­tics $ONCE, a com­pa­ny that has ef­fec­tive­ly helped a cat­e­go­ry of blind pa­tients see again.

“While im­me­di­ate readthrough (of the Sarep­ta da­ta) goes to LGMD2B and 2C, the promise goes be­yond LGMD. We think this is what ul­ti­mate­ly dri­ves long-term val­ue here as it makes the foun­da­tion be­hind Roche’s $4.8B Spark ac­qui­si­tion seem enor­mous­ly spec­u­la­tive and lim­it­ed in con­trast,” Sko­r­ney said.

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.

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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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.

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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Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

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.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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Den­mark's Gubra to col­lab­o­rate with Bay­er on pep­tides; Sam­sung and Bio­gen re­ceive FDA ap­proval for Lu­cen­tis biosim­i­lar

Danish biotech Gubra announced a research collaboration and license agreement with Bayer to develop peptide therapeutics to treat cardiorenal diseases. The collaboration will utilize Gubra’s peptide drug discovery platform to identify potential candidates.

This is not the first time Gubra has partnered with a company on peptide therapeutics — they partnered with Boehringer Ingelheim back in 2017 to create peptide therapeutics to treat obesity.

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.