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.”

Ven­ture Cap­i­tal as a Strate­gic Part­ner: Fu­el­ing In­no­va­tion be­yond Fi­nance

The average level of investment required for a biotech start-up to succeed is increasing every year, elevating the pressure even further on venture capital to make smart financial investments. Financial investment alone, however, does not always guarantee that exciting innovations can be transformed into real businesses that make a meaningful difference to patients.

Beyond just capital

At Astellas Venture Management (AVM) – a wholly-owned venture capital organization within Astellas, headquartered in the San Francisco Bay Area – capital is just one of the ingredients we offer to add value to our biotechnology investments and partnerships. We generally take a strategic investor approach for companies in our invested portfolio, providing access to expertise, technology and/or resources in addition to the injection of finance. An equity investment from AVM can include access to Astellas’ research and development (R&D) capabilities and expertise, and a global network of partner academic institutions and biotechnology companies, to help advance and accelerate the start-up’s innovation.

UP­DAT­ED: Ver­tex joins Mer­ck, Pfiz­er — re­vamp­ing multi­bil­lion-dol­lar tri­al strat­e­gy as biotech R&D crum­bles

You can add Pfizer, Merck and — as we found out Friday morning — Vertex to the growing list of pharma giants hitting the pause button on a range of clinical trials. But not everyone in R&D is getting a red light.

Vertex says that it’s doing its best to keep working its pipeline strategy, coming up with a plan “to enable virtual clinic visits and home delivery of study drug to ensure study continuity and medical monitoring, and to facilitate study procedures.”

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Covid-19 roundup: In­ter­cept, blue­bird and a grow­ing list of biotechs feel the pain as pan­dem­ic man­gles FDA, R&D sched­ules

Around 100 staffers at Boston area hospitals have now tested positive for Covid-19, spotlighting the growing risk that the pandemic will sideline many of the most essential workers in healthcare as caseloads peak in the US and around the globe. With more than 3,400 deaths, Spain has become the latest country to surpass the official death count attributed to the new coronavirus in China, where the outbreak originated. As of Thursday morning, confirmed global cases had crossed 470,000 and the death count eclipsed 21,000.

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Af­ter crit­ics lam­bast­ed Gilead for grab­bing the FDA's spe­cial rare drug sta­tus on remde­sivir, they're giv­ing it back

Two days after Gilead won orphan drug status for remdesivir as a potential treatment for Covid-19, they’re handing it back.

The company was slammed from several sides after Gilead reported that the FDA had come through with the special status, which comes with 7 years of market exclusivity, the waiver of FDA fees and some tax credits as well. Typically, everyone who can get orphan status lands it without much of a fuss, but Democratic presidential candidate Bernie Sanders, Public Citizen and other consumer groups were outraged.

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Mod­er­na CEO Stéphane Ban­cel out­lines a short path for emer­gency use of a coro­n­avirus vac­cine

NIAID director Anthony Fauci has left no doubts that it takes 12 to 18 months to get a new vaccine tested and in commercial use, in the best of circumstances. But in times of a global emergency — like these — maybe there’s another, faster route to follow.

In an SEC filing on Tuesday, Moderna $MRNA staked out a record-setting pathway to getting their mRNA vaccine into the frontline of the healthcare response as early as this fall. The SEC filing notes that CEO Stéphane Bancel told Goldman Sachs that an emergency use approval could allow the vaccine to go to healthcare workers and certain individuals in a matter of months — presumably provided the NIH sees the safety and efficacy data they would need from the Phase I.

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Caught in a Covid-19 mael­strom, Eli Lil­ly locks down clin­i­cal tri­als as multi­bil­lion-dol­lar R&D ops de­rail

The Covid-19 pandemic has derailed Eli Lilly’s $6 billion R&D operations.

The pharma giant reported Monday morning that it has decided to hit the brakes on most new study starts and pause enrollment for most ongoing studies. Lilly adds that it is continuing dosing for ongoing studies, “but with study-by-study consideration.”

The pandemic has severely disrupted healthcare systems around the globe, says Lilly, making it difficult or impossible to conduct studies at many research sites. And there’s no timeline for when it expects to get back on track.

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As share buy­backs come un­der scruti­ny, what's in store for the bio­phar­ma in­dus­try?

Stock buybacks are not to be permitted for companies that will be bailed out in the coronavirus stimulus package, Congressional leaders have signaled. To what degree the biopharma industry has relied on buybacks for earnings growth in recent years, and if the trend continues, are the big questions as scrutiny into the practice heightens and balance sheets weaken with the coronavirus pandemic wreaking havoc on global economies.

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A Sin­ga­pore VC rais­es $200M for a new round, but will Covid-19 pre­vent it from rais­ing the rest?

A top Singaporean biotech venture fund is nearly halfway toward its largest ever fund, but in a sign of what could be in store for VCs amid a global economic freeze, said they could face headwinds raising the other half.

Vickers Venture Partners has secured $200 million out of a targeted $500 million for its 6th fund, first announced in early 2018. They’ve given themselves 13 months to complete the financing, Vickers founder Finian Tan told Deal Street Asia, but the financial frost settling amid the Covid-19 pandemic could slow efforts.

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Strug­gling Unum ex­ecs are ready to con­sid­er a sale, merg­er or any deal that comes its way

Unum $UMRX is working its way through a survival plan of sorts.

After getting hit with a trio of FDA holds in its brief public history and triggering its second pivot to a new lead drug program while laying off 60% of the staff, the troubled penny stock biotech Unum Therapeutics has hatched new plans to secure financial backing while lining up a go-forward strategy for the company.

First, Lincoln Park Capital Fund has agreed to buy up to $25 million of the long-suffering stock, as Unum directs. And the executive team — led by CEO Chuck Wilson — has put everything on the table for consideration: a sale, acquisition, merger, licensing deal, you name it. The ACTR707 program, meanwhile, is being formally wrapped up — their second failed lead program.