Nello Mainolfi via YouTube

At­las-backed Kymera grabs $102M as its pro­tein degra­da­tion tech­nol­o­gy heads in­to clin­ic

When Bruce Booth and Nel­lo Main­olfi start­ed plan­ning a pro­tein degra­da­tion com­pa­ny, the field was open and sparse, dot­ted with a cou­ple of hope­ful star­tups and larg­er play­ers mak­ing ex­plorato­ry for­ays. Booth called it a “broad new modal­i­ty with plen­ty of free­dom to op­er­ate across po­ten­tial­ly every ther­a­peu­tic area and dis­ease state.”

Four years lat­er, Kymera Ther­a­peu­tics is look­ing to be­come one of the first of what will like­ly be many pro­tein degra­da­tion com­pa­nies to en­ter the clin­ic. The com­pa­ny an­nounced $102 mil­lion in Se­ries C fund­ing and a plan to bring its lead drug tar­get­ing IRAK4 in­to the first tri­als by next year. Biotech­nol­o­gy Val­ue Fund and Red­mile Group led the round.

“We are at the cusp of tran­si­tion­ing from a re­search to a de­vel­op­ment or­ga­ni­za­tion — or, I should say, to a re­search and de­vel­op­ment or­ga­ni­za­tion,” Main­olfi, now the CEO, told End­points News.  “This fi­nanc­ing re­al­ly al­lows to build to­ward the con­cept of build­ing a ful­ly in­te­grat­ed biotech com­pa­ny around pro­tein degra­da­tion, which I think is prob­a­bly one of the most trans­for­ma­tive modal­i­ties.”

As of to­day, Kymera would like­ly be the sec­ond biotech to bring a pro­tein de­grad­er in­to the clin­ic. A year ago, Arv­inas – whose founder Craig Crews pub­lished some of the first work show­ing how pro­tein degra­da­tion could be drugged — brought what it be­lieves to be the first pro­tein de­grad­er in­to hu­man test­ing, an an­dro­gen re­cep­tor-tar­get­ing drug for prostate can­cer. C4 Ther­a­peu­tics, the oth­er ma­jor start­up that ex­ist­ed when Kymera launched, has part­ner­ships with Bio­gen, Roche, and Dana-Far­ber, but no ther­a­pies in the clin­ic.

The pro­tein is a ki­nase im­pli­cat­ed in sev­er­al can­cers. Small mol­e­cules can in­hib­it IRAK4’s prop­er­ties as a ki­nase, but the pro­tein al­so func­tions as a scaf­fold­ing pro­tein that helps build the my­d­do­some pro­tein com­plex. The com­plex is sup­posed to be ac­ti­vat­ed to re­spond to in­fec­tion but can some­times ac­ti­vate aber­rant­ly, lead­ing to in­flam­ma­to­ry or au­toim­mune dis­ease.

The idea be­hind pro­tein degra­da­tion is that in­stead of send­ing a mol­e­cule to block the pro­tein’s ki­nase bind­ing site — and leav­ing the rest of the pro­tein in­tact and func­tion­ing — re­searchers can re­move the pro­tein en­tire­ly. They do this by hi­jack­ing the body’s in­ter­nal sys­tem to re­move pro­teins that are mis­fold­ed or are in over­abun­dance. En­zymes called E3 lig­as­es tag un­want­ed pro­teins with a pro­tein called ubiq­ui­tin, like a gen­er­al pick­ing tar­gets for an air raid. Those tagged pro­teins are then tar­get­ed by pro­teas­es and un­fold­ed in the body’s mul­ti-step garbage dis­pos­al sys­tem.

Kymera us­es small mol­e­cules to drag E3 lig­as­es to the pro­tein it wants to elim­i­nate. Their pre­clin­i­cal re­search sug­gests re­mov­ing IRAK4 in this way will help treat a rare in­flam­ma­to­ry skin con­di­tion called hidradeni­tis sup­pu­ra­ti­va and B-cell lym­phomas, among oth­er dis­eases. They al­so have pro­grams tar­get­ing the tran­scrip­tion fac­tor STAT3, which is part of the JAK path­way.

Main­olfi said the gen­er­al con­cept had been ap­par­ent for years, but ad­vance­ments around 2016 made it look fea­si­ble.

“This is tech­nol­o­gy that has fas­ci­nat­ed me for years, but what was lack­ing were re­al­ly the chem­i­cal tools,” Main­olfi said.

Since then, Kymera has built up a plat­form they say dif­fer­en­ti­ates them from some of their com­peti­tors by us­ing in­for­mat­ics to iden­ti­fy new E3 lig­as­es and the best drugs in im­munol­o­gy and on­col­o­gy. And last year they signed a $70 mil­lion col­lab­o­ra­tion with Ver­tex. Main­olfi, who stepped in­to the CEO job in No­vem­ber af­ter Lau­rent Au­doly’s de­par­ture, said it helps them ap­ply their tech­nol­o­gy in in­di­ca­tions be­yond the two they’ve fo­cused on to date.

Even­tu­al­ly, he said, pro­tein degra­da­tion is go­ing to be every­where.

“When I look at pro­tein degra­da­tion, I look at a field just like an­ti­body or RNA ther­a­peu­tics 20 years ago,” Main­olfi said. “It is a field that will trans­form med­i­cine.”

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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Image: Shutterstock

MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.

Isao Teshirogi, Shionogi president and CEO (Kyodo via AP Images)

Sh­ionogi's Covid an­tivi­ral lands first ap­proval in Japan's new emer­gency ap­proval path­way

Japanese regulators on Tuesday signed off on Shionogi’s homegrown antiviral for Covid-19, known as Xocova (ensitrelvir), making it the first approval under Japan’s emergency regulatory approval system.

The emergency approval, following a back-and-forth with regulators since last February, is based on a safety profile with more than 2,000 patients who have accessed the pill, and clinical symptomatic efficacy for five typical Omicron-related symptoms (primary endpoint) and antiviral efficacy (key secondary endpoint) in patients with mild to moderate SARS-CoV-2 infection, regardless of risk factors or vaccination status, and during the Omicron-dominant phase of the pandemic.

Karen Aiach, Lysogene CEO (RE(ACT) Discovery Institute)

Gene ther­a­py flunks PhII/III study, but for­mer Sarep­ta part­ner sees a path for­ward — if it can find the cash

The development path for Lysogene’s gene therapy for MPS IIIA has been a rocky one. After the FDA slapped a partial clinical hold on a Phase II/III study, a patient already dosed in the trial died, although it was deemed unrelated to treatment. Then earlier this year, Sarepta pulled out of their three-year partnership due to disagreements on who will handle commercial supply.

And now, Lysogene reported the trial has failed its primary endpoint.

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Dermavant Sciences' first consumer TV ad for its Vtama psoriasis med shows people ready for a new topical treatment.

Roivant’s Der­ma­vant de­buts first-ever TV com­mer­cial for pso­ri­a­sis cream Vta­ma

Dermavant Sciences has been marketing its first product, psoriasis med Vtama, to dermatologists for months, but on Tuesday it rolled out its first consumer campaign. The debut DTC effort including a streaming TV commercial encourages patients to a “Topical Uprising” in a nod to Vtama being a topical cream.

In the new commercial, a swell of people discards scarves and jacket coverings, gathering in the street to converge on a pharmacy to demand a steroid-free prescription. A moment of levity follows when a pharmacist says, “You know you can just talk to your doctor, right?” The gathered crowds collectively says, “Oh.”

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