Tar­get­ing CD47? UCLA joins band­wag­on, with gel to stem tu­mors from resur­fac­ing

Hit­ting the “don’t eat me” CD47 re­cep­tor tar­get has gal­va­nized an army of drug de­vel­op­ers who want to make in­roads in the bur­geon­ing field of can­cer im­munother­a­py by off­set­ting im­muno­sup­pres­sion. But in an ef­fort to sub­vert side ef­fects that can be caused by the sys­temic ab­sorp­tion of such an­tag­o­nists, re­searchers are test­ing a gel that could be sprayed on pa­tients who have un­der­gone surgery to in­hib­it tu­mor re­cur­rence and metas­ta­sis.

A biodegrad­able fib­rin gel, which en­cap­su­lates cal­ci­um car­bon­ate nanopar­ti­cles pre-loaded with an an­ti-CD47 an­ti­body, was used by a team of re­searchers led by Zhen Gu, a pro­fes­sor of bio­engi­neer­ing at the UCLA Samueli School of En­gi­neer­ing. Fol­low­ing tu­mor re­sec­tion in mice with ad­vanced melanoma, the gel was sprayed on to the sur­gi­cal site to cur­tail the growth of tu­mor cells that lin­gered de­spite surgery. Half the mice in the study did not see their tu­mors re-emerge 60 days fol­low­ing treat­ment, da­ta showed.

Zhen Gu

Cal­ci­um car­bon­ate — the main com­po­nent of egg shells — was cho­sen due to its abil­i­ty to be grad­u­al­ly dis­solved in sur­gi­cal wound sites, which are slight­ly acidic, and be­cause it boosts macrophage ac­tiv­i­ty, said the study’s lead au­thor Qian Chen, a post­doc­tor­al re­searcher at UCLA.

A pletho­ra of drug de­vel­op­ers in­clud­ing Alexo Ther­a­peu­tics, Arch On­col­o­gy, Au­ri­gene, Blink Bio­med­ical, Cel­gene, Forty Sev­en, Novim­mune, OSE Im­munother­a­peu­tics, Sor­ren­to, Syn­thon Hold­ing and Tril­li­um Ther­a­peu­tics, are de­vel­op­ing CD47 an­tag­o­nists in the hope of scram­bling the “don’t eat me” sig­nal that can­cer cells are de­pen­dent on to evade macrophages.

Qian Chen

But the oc­cur­rence of ane­mia and throm­bo­cy­tope­nia caused by sys­temic ad­min­is­tra­tion of such an­tag­o­nists-in-de­vel­op­ment re­mains a con­cern, the UCLA team wrote in their peer re­viewed study pub­lished in Na­ture Nan­otech­nol­o­gy.

Many can­cer pa­tients un­der­go surgery to up­root tu­mors, but of­ten the can­cer re-emerges. This re­search sug­gests the im­munother­a­peu­tic fib­rin gel can “awak­en” the im­mune sys­tem by re-arm­ing macrophages at the sur­gi­cal site to chew up can­cer cells.

“We al­so learned that the gel could ac­ti­vate T cells in the im­mune sys­tem to get them to work to­geth­er as an­oth­er line of at­tack against lin­ger­ing can­cer cells,” Chen added in a state­ment.

The team of sci­en­tists in­tends to test this ap­proach in an­i­mal tri­als to de­ter­mine the ide­al mix of nanopar­ti­cles, op­ti­mal dos­ing and treat­ment fre­quen­cy, be­fore grad­u­at­ing to hu­man test­ing.


Im­age: SHUT­TER­STOCK

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: Chi­na's BeiGene scores first-ever FDA ap­proval — but can they carve up J&J's block­buster fran­chise?

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,500+ biopharma pros reading Endpoints daily — and it's free.

Carson Block. Muddy Waters via YouTube

Shorts ga­lore: Mud­dy Wa­ters sees slide for Pep­tiDream, tweets con­cerns about Fi­bro­Gen's new da­ta

The short seller Muddy Waters is taking aim at Japan’s most profitable biotech, projecting a slide for a company that has skyrocketed over the last four years. Meanwhile, the firm tweeted out an analysis accusing FibroGen of manipulating data to obscure safety concerns in their latest reveal, although some investors seem satisfied by the biotech’s explanation.

Muddy Waters shorted PeptiDream, a Japanese biotech-for-hire that leveraged its peptide library into partnerships with some of the world’s largest pharmaceutical companies, a 50% profit margin and $6 billion valuation. The firm noted that despite its esteem, PeptiDream has failed to bring a drug to market 13 years after its 2006 launch (although this is not especially rare for biotech).

Pin­cer move­ment: Cal­i­for­nia biotech gets $35M to suf­fo­cate can­cer in co­or­di­nat­ed at­tack

Having served in Afghanistan, the navy veteran leading California-based EpicentRx wants to leave no patient behind with his arsenal of anti-cancer drugs. On Thursday, the company was given a $35 million boost to further its mission.

The injection of funds will be used to shepherd its late-stage CD47 drug, RRx-001, to the FDA for marketing, and its oncolytic virus program into the clinic.

RRx-001, engineered as an agent that makes tumor cells more sensitive to therapy, is in a Phase III trial in combination with chemotherapy for use in third-line and beyond small cell lung cancer (SCLC). The drug has been granted orphan drug designation from FDA for SCLC, neuroendocrine cancer and glioblastoma.