NIH re­searchers re­port an­i­mal mod­el val­i­da­tion for stem cell-based ap­proach to ad­vanced dry AMD

A group of NIH re­searchers say they have laid the ground­work need­ed to tack­le the root cause of an ad­vanced form of age-re­lat­ed mac­u­lar de­gen­er­a­tion by re­pro­gram­ming adult blood cells in­to reti­nal cells in rat and pig mod­els. And now they plan to move that in­to an his­toric break­through ef­fort in hu­mans.

The sci­en­tists from the NIH’s Na­tion­al Eye In­sti­tute set out to pre­vent blind­ness in ge­o­graph­ic at­ro­phy, or ad­vanced dry AMD. Reti­nal pig­ment ep­ithe­lial cells nur­ture pho­tore­cep­tors; when they die (usu­al­ly in the ear­ly stage of ge­o­graph­ic at­ro­phy) the pho­tore­cep­tors lose pro­tec­tion and even­tu­al­ly die as well, ul­ti­mate­ly re­sult­ing in blind­ness. With the re­sults and pro­to­cols de­tailed in a Sci­ence Trans­la­tion­al Med­i­cine pa­per to­day, they are hop­ing to set the stage for a first-in-hu­man study.

The cells used in the au­tol­o­gous treat­ment goes through three stages: They be­gin as a pa­tient’s blood cells, get con­vert­ed in­to in­duced pluripo­tent stem cells (iP­SCs), and are fi­nal­ly pro­grammed to be­come reti­nal pig­ment ep­ithe­lial (RPE) cells and thin­ly lay­ered on a scaf­fold. RPE cells nur­ture pho­tore­cep­tors; their death marks the ear­ly stage of ge­o­graph­ic at­ro­phy, al­so known as ad­vanced dry AMD.

By patch­ing in iP­SC-de­rived RPE cells to re­place the dy­ing ones, re­searchers the­o­rized they could keep the pho­tore­cep­tors — light-sens­ing cells — func­tion­ing prop­er­ly, thus main­tain­ing vi­sion.

As far as they could tell, it worked.

Kapil Bhar­ti, lead in­ves­ti­ga­tor for the an­i­mal study

“Ten weeks af­ter the hu­man iP­SC-de­rived RPE patch­es were im­plant­ed in the an­i­mals’ reti­nas, imag­ing stud­ies con­firmed that the lab-made cells had in­te­grat­ed with­in the an­i­mal reti­na,” a re­lease reads. The lab-made cells al­so grew ma­ture enough to keep the pho­tore­cep­tors alive and healthy.

The re­searchers al­so checked to make sure the RPE cells they grew had no ge­net­ic mu­ta­tions linked to can­cer growth, a “key con­cern with any stem cell ther­a­py.”

The lead­ing cause of blind­ness among the el­der­ly af­fect­ing more than 5 mil­lion world­wide, ge­o­graph­ic at­ro­phy has once in­spired megablock­buster dreams at Roche for its eye drug lam­pal­izum­ab — which was qui­et­ly scraped af­ter fail­ing both Phase II­Is. Ken­tucky-based biotech Apel­lis has more en­cour­ag­ing da­ta with its com­ple­ment C3 in­hibitor. With an IND pend­ing, stem cell-based ther­a­py will soon be­come an­oth­er can­di­date to claim the first ap­proved treat­ment for the dis­ease.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology

ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development

CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

Ted Ashburn. Oncorus

Cowen, Per­cep­tive lead $79.5M Se­ries B for 's­tand­out' biotech shep­herd­ing on­colyt­ic virus to clin­ic

As several Big Pharma players secure biotech partners in the oncolytic virus space for new immuno-oncology combos, Cowen and Perceptive Advisors have come out with their own bet on a startup that promises to shine.

The marquee investors are joining MPM, Deerfield, Celgene, Astellas, Arkin and UBS in backing the drug developer, Oncorus, which will now deploy the $79.5 million in Series B cash toward clinical development of its lead program. Other new investors include Surveyor Capital, Sphera Funds, IMM Investment, QUAD Investment Management, UTC Investment, SV Investment Corp and Shinhan Investment-Private Equity, the last five of which are Korean-based funds.

Fu­til­i­ty analy­sis au­gurs de­feat in piv­otal tri­al test­ing of Nu­Cana's lead drug in metasta­t­ic pan­cre­at­ic can­cer

Nearly two years after making its public debut, UK-based NuCana’s mission to make chemotherapies more potent and safer was dealt a blow, after a pivotal study testing its lead experimental drug halted enrollment in a hard-to-treat advanced form of cancer, following a futility analysis.

The drug, Acelarin, is being evaluated for use in metastatic pancreatic cancer patients who were not considered suitable for combination chemotherapy. In the late-stage ACELARATE study — which compared the experimental drug against the chemotherapy gemcitabine — 200 patients had been enrolled by the sponsor, Clatterbridge Cancer Centre, before an analysis from an independent safety and data monitoring panel suggested the study’s main goal would not be met.

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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