As R&D set­backs mul­ti­ply, a pi­o­neer­ing CRISPR/Cas9 pro­gram for Duchenne MD con­tin­ues to im­press in new dog study

While one drug af­ter the next seems to get reg­u­lar­ly shot down in Duchenne mus­cu­lar dy­s­tro­phy, as we saw to­day with Pfiz­er’s failed Phase II, a pre­clin­i­cal CRISPR gene edit­ing pro­gram has been mak­ing some im­pres­sive progress in an­i­mal stud­ies.

Thurs­day af­ter­noon, Ex­on­ics pro­vid­ed some in­trigu­ing de­tails to show how their gene-edit­ing ap­proach works in dogs. Dis­patch­ing a Cas9 scalpel with guide RNA in­side an AAV de­liv­ery ve­hi­cle straight to mus­cle cells, the re­searchers say that their ap­proach was able to re­store dy­s­trophin pro­duc­tion that reached up to 92% of nor­mal in a ca­nine mod­el for the dis­ease.

That was for the high­est dose used.

John Rip­ple

“Typ­i­cal­ly,” Ex­on­ics CEO John Rip­ple tells me, the re­sponse in dy­s­trophin pro­duc­tion “was above 50%.”

That’s a big deal, he says, par­tic­u­lar­ly when re­searchers in the field see pa­tients turn asymp­to­matic at around 20% of nor­mal dy­s­trophin pro­duc­tion.

Ex­on­ics has been mak­ing mea­sured ad­vances in this field, start­ing with the lab work done by UT South­west­ern’s Er­ic Ol­son, who did the ear­ly sci­en­tif­ic in­ves­ti­ga­tion us­ing CRISPR on cells and mice. We made con­tact ear­ly on, as he dis­cussed the progress he had been mak­ing. Ol­son co-au­thored the study out to­day.

“Ca­nines have clin­i­cal and patho­log­i­cal fea­tures sim­i­lar to the hu­man pre­sen­ta­tion of Duchenne, in­clud­ing mus­cle weak­ness, at­ro­phy and fi­bro­sis,” Ol­son not­ed to­day, as the lat­est work ap­peared in Sci­ence.

Late last year a $40 mil­lion launch round helped the com­pa­ny get start­ed with a vir­tu­al crew, which is now grow­ing fast. From a hand­ful of staffers, Ex­on­ics ros­ter has now grown to 11, with plans to dou­ble that when they move in­to a new lab and of­fices in Wa­ter­town lat­er this year. 

In many ways, Duchenne MD could prove one of the best fields for a CRISPR team to work in — es­pe­cial­ly in the ear­ly days.

In this case, they’re look­ing for a sim­ple cut and re­pair re­sponse need­ed to cor­rect er­rant cells that trig­ger the ail­ment, which slow­ly but sure­ly crip­ples and then kills its vic­tims. Tar­get­ing mus­cles and heart tis­sue gives them a sta­ble group of non-di­vid­ing cells to work with, which may well re­duce the chances of any off-tar­get im­pact — a top­ic that rou­tine­ly sparks near pan­ic in CRISPR/Cas9 in­vest­ment cir­cles.

It should be not­ed, though, that be­fore we start spot­light­ing a po­ten­tial cure for Duchenne, or spe­cif­ic ge­net­ic pa­tient pop­u­la­tions with the dis­ease, the drug is still not ready for a prime time hu­man tri­al.

“Our next step is to con­tin­ue pre­clin­i­cal work, ad­vanc­ing in the clin­ic,” adds the CEO. “We need to do longer an­i­mal stud­ies, main­tain dy­s­trophin pro­tein over a long pe­ri­od of time.”

That way, by the time they sit down with reg­u­la­tors and start talk­ing hu­man stud­ies, they’ll be able to make a sol­id case built on ex­ten­sive pre­clin­i­cal work. When­ev­er that day ar­rives.

There’s not an un­lim­it­ed amount of time avail­able, though. Pa­tients are still in des­per­ate need, and oth­er biotechs are al­so work­ing on a cure.

Ex­on­ics is one of sev­er­al de­vel­op­ers look­ing to carve a new re­search path to this dis­ease. Mus­cle drugs have proven very prob­lem­at­ic in ad­dress­ing a se­vere dis­ease like this. And Sarep­ta’s eteplirsen was ap­proved with­out sig­nif­i­cant ef­fi­ca­cy da­ta, un­der­scor­ing a dra­mat­ic need for new drugs. Sarep­ta, Sol­id Bio and oth­ers are ex­plor­ing gene ther­a­py ap­proach­es, which have al­so high­light­ed some im­pres­sive ear­ly re­sults.


Im­age: Er­ic Ol­son. Jane Cof­fin Childs Memo­r­i­al Fund for Med­ical Re­search

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

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How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

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An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

(Photo courtesy Pfizer)

FDA's vac­cine ad­comm votes al­most unan­i­mous­ly in fa­vor of Pfiz­er's Covid-19 vac­cine for younger chil­dren

The FDA’s Vaccines and Related Biological Products Advisory Committee on Tuesday voted 17-0, with one panelist abstaining, that the benefits of the Pfizer-BioNTech Covid-19 vaccine outweigh the risks for children between the ages of five and 12.

The vote will likely trigger a process that could allow the shots to begin rolling out as early as next week.

The vaccine, which is one-third of the adult Pfizer dose, proved to be about 90% effective in a placebo-controlled trial in which about 1,500 kids in this age range received the vaccine, and only about 12% of those receiving the vaccine had any adverse event. All serious adverse events in the trial were unrelated to the vaccine.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Mod­er­na chips in fur­ther on African vac­cine sup­ply — but ad­vo­cates are call­ing for even more

In a sign of its growing commitment to the continent, Moderna will supply up to 110 million doses of its Covid-19 vaccine to the African Union, the company announced Tuesday. And CEO Stéphane Bancel said it’s just the first step.

“We believe our vaccine can play an important role in addressing the needs of low-income countries given its combination of high Phase 3 efficacy against COVID-19, strong durability in the real-world evidence, and superior storage and handling conditions. We recognize that access to COVID-19 vaccines continues to be a challenge in many parts of the world and we remain committed to helping to protect as many people as possible around the globe,” Bancel said in a statement.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

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Ugur Sahin, AP Images

As pres­sure to share tech­nol­o­gy mounts, BioN­Tech se­lects Rwan­da for lat­est vac­cine site

BioNTech’s first mRNA-based vaccine site in Africa will call Rwanda home, and construction is set to start in mid-2022, the company announced Tuesday at a public health forum.

The German company signed a memorandum of understanding, after a meeting between Rwanda’s Minister of Health, Daniel Ngamije, Senegal’s Minister of Foreign Affairs Aïssata Tall Sall, and senior BioNTech officials. Construction plans have been finalized, and assets have been ordered. The agreement will help bring end-to-end manufacturing to Africa, and as many as several hundred million doses of vaccines per year, though initial production will be more modest.