A knock­down-and-re­place gene ther­a­py from Penn re­searchers shows promise in rare eye dis­ease

It’s been a year of great strides in gene ther­a­py, with Spark’s Lux­tur­na earn­ing the first US reg­u­la­to­ry ap­proval in the field for in­her­it­ed blind­ness. Now, re­searchers at Uni­ver­si­ty of Penn­syl­va­nia might be able to add to that suc­cess with a new gene ther­a­py that’s shown promise tack­ling a group of eye prob­lems called re­tini­tis pig­men­tosa.

This rare con­di­tion changes how the reti­na re­sponds to light, mak­ing it hard for peo­ple to see — es­pe­cial­ly af­fect­ing night vi­sion and pe­riph­er­al vi­sion. And it gets worse over time, some­times lead­ing to near-blind­ness. Sci­en­tists have iden­ti­fied more than 150 mu­ta­tions of the light-sens­ing mol­e­cule rhodopsin, which all lead to the dis­ease. How­ev­er, those re­searchers at Penn in­tend to de­vel­op a treat­ment that works re­gard­less of the mu­ta­tion. They’ve pub­lished their ear­ly-stage find­ings in this week’s Pro­ceed­ings of the Na­tion­al Acad­e­my of Sci­ences.

“It’s a one treat­ment fits all,” says William Bel­tran, pro­fes­sor of oph­thal­mol­o­gy and di­rec­tor of the Di­vi­sion of Ex­per­i­men­tal Reti­nal Ther­a­pies at Penn Vet and co-lead au­thor of the study. “The treat­ment tar­gets a re­gion of the rhodopsin gene that is ho­mol­o­gous in hu­mans and dogs and is sep­a­rate from where the mu­ta­tions are lo­cat­ed. That gives us great hope about mak­ing this a trans­la­tion­al treat­ment.”

The re­searchers, from Penn’s School of Vet­eri­nary Med­i­cine and Perel­man School of Med­i­cine, col­lab­o­rat­ed with sci­en­tists at the Uni­ver­si­ty of Flori­da to de­vel­op a ther­a­py that ba­si­cal­ly knocks down the ab­nor­mal copy of rhodopsin and then re­places it with a healthy copy. This method has worked in dogs, they say, which can de­vel­op a very sim­i­lar dis­ease as hu­mans.

“What we showed was that if you just did the knock­down alone, you pre­serve the out­er nu­clear lay­er of rods, which is where the cell bod­ies are lo­cat­ed,” Bel­tran said. “But with­out an­oth­er crit­i­cal lay­er, the out­er seg­ments, where rhodopsin plays the es­sen­tial role of cap­tur­ing light and ini­ti­at­ing vi­sion, then the rods be­come use­less. How­ev­er, if you com­bine the knock­down with the re­place­ment reagents, then the dras­tic dif­fer­ence is that you now have per­fect­ly formed and aligned out­er seg­ments and func­tion­al pho­tore­cep­tor cells.”

So far, track­ing the treat­ment ef­fect more than eight months af­ter de­liv­ery of the gene ther­a­py, the ef­fect seems sta­ble and last­ing. The re­search team is cur­rent­ly work­ing to move the find­ings in­to clin­i­cal tri­als.

Ar­tur Cide­ciyan, re­search pro­fes­sor of oph­thal­mol­o­gy at Penn Med­i­cine, was the co-lead au­thor of the study.


Im­age: William Bel­tran, Ar­tur Cide­ciyan, Gus­ta­vo Aguirre, and Samuel Ja­cob­son were part of the joint team from Penn Vet and Penn Med­i­cine who led the work. PEN­NVET

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.