Laurent Audoly, Parthenon CEO

Can new drugs punch holes in can­cer's pro­tec­tive bar­ri­er? For Parthenon Ther­a­peu­tics, that's the $65M ques­tion

Imag­ine tak­ing an ice pick to the pro­tec­tive bar­ri­er that sur­rounds can­cer cells. That’s es­sen­tial­ly what Parthenon Ther­a­peu­tics is try­ing to do — and now a hand­ful of in­vestors in­clud­ing Pfiz­er’s ven­ture arm are putting up $65 mil­lion to see it through.

“For at least 50% of tu­mors out there, can­cer ther­a­pies or can­cer fight­ing cells are un­able to pen­e­trate the tu­mor be­cause of a phys­i­cal bar­ri­er,” CEO Lau­rent Au­doly told End­points News. “When we did our re­search, we quick­ly re­al­ized that this was a wide open op­por­tu­ni­ty.”

Au­doly, the for­mer CEO of Kymera, launched Parthenon in the sum­mer of 2019 to find new ways of re­pro­gram­ming the tu­mor mi­croen­vi­ron­ment to at­tack can­cer cells’ pro­tec­tive shields. And Wednes­day, he and his team un­veiled a siz­able Se­ries A round led by North­pond Ven­tures, Pfiz­er Ven­tures and Tai­ho Ven­tures.

Re­search sug­gests there are sev­er­al types of bar­ri­ers that un­der­pin im­mune cell ex­clu­sion, Au­doly ex­plained. Most com­pa­nies are pur­su­ing ways around a con­cept that sci­en­tists have dubbed “dy­nam­ic bar­ri­ers,” or im­munol­o­gy-based bar­ri­ers which pre­vent the body’s im­mune sys­tem from de­stroy­ing the tu­mor. A large crowd of im­muno-on­col­o­gy com­pa­nies big and small fall un­der this um­brel­la, with the num­ber of drugs in the clin­ic swelling over the last few years. In the case of Mer­ck and its block­buster Keytru­da, for ex­am­ple, PD-1 is a type of dy­nam­ic bar­ri­er, ac­cord­ing to Au­doly.

Then there are func­tion­al bar­ri­ers, in which the core of the tu­mor gen­er­ates re­pel­lents against im­mune cells that could de­stroy the tu­mor. There’s al­so what’s called a phys­i­cal or me­chan­i­cal bar­ri­er, which Au­doly says is akin to barbed wire built around the core of a tu­mor, which pre­vents im­mune cells and some an­ti­tu­mor agents from pen­e­trat­ing the cells. This is the type of bar­ri­er that Parthenon is most fo­cused on, in ad­di­tion to func­tion­al bar­ri­ers.

Their ap­proach is sim­ple: “Think of it as, for ex­am­ple, an ice­break­er that is mak­ing its way across the ice sheets. And then be­hind that, there are a num­ber of ships with their pre­cious car­go that can then reach the des­ti­na­tion,” Au­doly said.

On Wednes­day, some of Parthenon’s col­lab­o­ra­tors pub­lished a piece in Na­ture de­scrib­ing one of the com­pa­ny’s ap­proach­es with its lead pro­gram PRTH-101 — neu­tral­iz­ing dis­coidin do­main re­cep­tor 1 (DDR1), a col­la­gen re­cep­tor that’s be­lieved to play a role in sta­bi­liz­ing the tu­mor ex­tra­cel­lu­lar ma­trix. Re­searchers showed in pre­clin­i­cal mod­els that by neu­tral­iz­ing DDR1, they could per­fo­rate the tu­mor’s pro­tec­tive bar­ri­er in triple neg­a­tive breast can­cer.

“That is not the on­ly type of tu­mor… that we’re go­ing to go af­ter,” Au­doly said. “We be­lieve that there are many oth­er op­por­tu­ni­ties be­sides this one can­cer type for our pipeline.”

The chief ex­ec­u­tive wasn’t ready to of­fer a time­line on the com­pa­ny’s path to­ward the clin­ic, but said the Se­ries A funds will be used to grow the 10-per­son team and scale the plat­form. In a year from now, he ex­pects to have 25 to 30 staffers.

“We were a com­pa­ny that was re­al­ly found­ed in­to so-called wilder­ness,” he said. “We’re founders that came to­geth­er be­cause of our strong be­lief that there are op­por­tu­ni­ties for pa­tients liv­ing with can­cers that are ba­si­cal­ly not be­ing ad­vanced in­to the clin­ic.”

What’s next? Au­doly and his team will keep chip­ping away at the pipeline, one chunk at a time.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Radek Spisek, Sotio CEO (Cellestia)

A qui­et Czech biotech bags $315M to dri­ve its blos­som­ing can­cer pipeline through the clin­ic

In the rather insular world of biotech, most innovation inevitably comes from a cluster of R&D hubs — Cambridge, San Francisco, etc. But sometimes success stories sprout from rocky soil, which is most certainly the case with Prague-based Sotio Biotech and its suddenly jam-packed pipeline of cancer drugs.

After years in quiet development, Sotio now has $315 million in new funds to play with from parent company PPF Group, an investment group founded in the Czech Republic, as the biotech looks to advance its growing pipeline through early- and mid-stage trials.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.