At­las-in­cu­bat­ed Kymera leaps out of stealth mode, joins the hunt for game-chang­ing pro­tein degra­da­tion drugs

Pro­tein degra­da­tion R&D isn’t new. Jay Brad­ner launched C4 Ther­a­peu­tics to blaze the pro­tein degra­da­tion ap­proach just be­fore he took the helm at the No­var­tis In­sti­tute of Bio­med­ical Re­search, then re­cent­ly formed a dis­cov­ery al­liance with UC Berke­ley with the same ba­sic ap­proach in mind. Arv­inas al­so has cen­tered on pro­tein degra­da­tion, build­ing on the lab work of Yale’s Craig Crews.

But to­day there’s an­oth­er start­up join­ing the pi­o­neers called Kymera, and the Cam­bridge, MA-based play­er is com­ing out of stealth mode to­day with a $30 mil­lion launch round and a de­vel­op­ment strat­e­gy cre­at­ed on the no­tion that there’s plen­ty of vir­gin ter­ri­to­ry for every­one to ex­plore.

Nel­lo Main­olfi

Nel­lo Main­olfi, a No­var­tis vet, Kymera co-founder and chief tech­nol­o­gy of­fi­cer, says it start­ed back when he was sit­ting in Bruce Booth’s At­las Ven­ture of­fice in late 2015 dis­cussing the best way to jump in­to the pro­tein degra­da­tion field — look­ing for ways to de­risk tar­get se­lec­tion and go af­ter some break­through ther­a­pies with game-chang­ing po­ten­tial.

That con­ver­sa­tion would lead to some in­ter­changes with some of the aca­d­e­mics at work in the field — we’ll hear more about who that is at a lat­er point — while they built a tool­box that could be used to ef­fi­cient­ly de­grade spe­cif­ic pro­teins of in­ter­est.

The con­cept be­hind these pro­grams sounds sim­ple enough. Where pro­tein in­hi­bi­tion has cre­at­ed some ad­vanced meds — specif­i­cal­ly for dis­eases like prostate and breast can­cer — de­grad­ing them could prove to be a much more durable so­lu­tion. Hi­jack­ing the body’s ubiq­ui­tin-pro­tea­some sys­tem that’s used to dis­pose of pro­teins, bind­ing to pro­teins and mark­ing them for de­struc­tion, they’re build­ing a plat­form that can be used to stymie any dis­ease-caus­ing pro­tein. But Booth notes that jump­ing from in­hi­bi­tion to degra­da­tion re­quires adding a third part to the equa­tion, a math prob­lem re­lat­ed to an en­dur­ing cat­alyt­ic de­struc­tion of the tar­get.

And that’s re­al­ly not sim­ple at all. Booth wrote a blog about this, which ex­plains the whole process in clear terms.

Over the past 18 months, the team at Kymera has grown to 12, and they’ve been us­ing the seed cash to start the pre­clin­i­cal work need­ed to iden­ti­fy the first pro­gram to take in­to the clin­ic.

Lau­rent Au­doly

Lau­rent Au­doly, an­oth­er Big Phar­ma vet­er­an who jumped from his job as R&D chief at Pierre Fab­ry to take the CEO’s post, says it’s still too ear­ly to say ex­act­ly what dis­ease tar­gets they’re go­ing af­ter, but all three of the prin­ci­pals are hap­py to iden­ti­fy the toll-like re­cep­tor and in­ter­leukin-1 path­way as their ini­tial fo­cus. And the new CEO plans to dou­ble the size of the staff over the course of the next year.

The goal, says Au­doly, is to “mine a path­way in a very sys­tem­at­ic man­ner.”

Kymera has all the clas­sic ear­marks of a Bruce Booth spe­cial. He brought in two cor­po­rate ven­ture funds — Am­gen and Lil­ly Ven­tures — to fund the A round af­ter some ef­fi­cient in­cu­ba­tion work. Lab space was pro­vid­ed by Lab­Cen­tral, which came with a “Gold­en Tick­et” from J&J/JLABS. And like many At­las star­tups, Booth and his col­leagues will have al­ready be­gun the work of lin­ing up some mar­quee part­ners to do the work with — stan­dard op­er­at­ing pro­ce­dure for plat­form com­pa­nies with a lot of po­ten­tial drug tar­gets to work with.

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive PhI­II for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma. 

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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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 help@endpointsnews.com with any issues.

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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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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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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

UP­DAT­ED: 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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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.