Shelia Violette (Q32)

For a post-Soliris world, At­las-backed Q32 Bio out­lines $46M next-gen com­ple­ment play

Long be­fore Alex­ion kin­dled a re­nais­sance of com­ple­ment ther­a­peu­tics with the in­tro­duc­tion of the first an­ti-C5 an­ti­body, Mike Holers — a long­time pro­fes­sor at the Uni­ver­si­ty of Col­orado School of Med­i­cine — be­came fas­ci­nat­ed with the host de­fense sys­tem as he com­plet­ed his rheuma­tol­ogy train­ing. As Soliris be­gins to fade and fol­low-on, ri­vals and even gener­ics catch up to the stan­dard bear­er. Holers is de­but­ing a next-gen­er­a­tion ap­proach he’s been re­fin­ing with At­las Ven­ture over the last two years.

Fund­ed with $46 mil­lion pro­vid­ed by At­las as well as Or­biMed, Abing­worth and Sanofi Ven­tures, Q32 wants to bring the first tis­sue-tar­get­ed com­ple­ment drugs in­to the clin­ic by the end of 2021. The CU Health­care In­no­va­tion Fund and Chil­dren’s Hos­pi­tal Col­orado are al­so in­vestors.

Michael Holers

Over his years of re­search and col­lab­o­ra­tion with col­league Joshua Thur­man and Steven Tom­lin­son at the Med­ical Uni­ver­si­ty of South Car­oli­na, Holers told End­points News, the com­ple­ment field has evolved to re­veal tar­gets that can help sci­en­tists ze­ro in on dis­eased tis­sue, rather than block­ing com­ple­ment ac­ti­va­tion sys­tem­i­cal­ly.

When you think through how the com­ple­ment sys­tem func­tions, you see “a lot of high lev­els of sys­temic pro­teins, but its re­al tis­sue in­jury, its re­al dam­age is lo­cal­ized to cells and tis­sues on the sur­face of cells, in the in­ter­sti­tium,” he said.

Yet know­ing how to di­rect drugs to the right places wasn’t enough, as his ex­pe­ri­ence with a pre­vi­ous start­up dubbed Tal­i­gen — which had an ear­ly tis­sue tar­get­ing tech­nol­o­gy that was ac­quired but ul­ti­mate­ly re­tired by Alex­ion — showed. You al­so need deep knowl­edge in pro­tein en­gi­neer­ing to make sure you’re rein­ing in the com­ple­ment sys­tem prop­er­ly.

That’s where At­las and She­lia Vi­o­lette, Q32’s co-founder, CSO and pres­i­dent of re­search, comes in.

Rather than an­ti­bod­ies, they are work­ing on fu­sion pro­teins that grab the tis­sue-spe­cif­ic tar­gets on one end and car­ries a nat­u­ral­ly oc­cur­ring pro­tein that nor­mal­ly keeps the sys­tem in check.

“One of the things that is now bet­ter un­der­stood is that across pret­ty much any dis­ease where com­ple­ment ac­ti­va­tion be­comes dys­reg­u­lat­ed, it’s be­cause you’re los­ing the op­ti­mal func­tion of those neg­a­tive reg­u­la­tor pro­teins,” Vi­o­lette, who left a lengthy ca­reer at Bio­gen to be­come At­las’ en­tre­pre­neur-in-res­i­dence in 2016, said.

It’s so cen­tral to what they do that the start­up re­named it­self from Ad­mirx to Q32, draw­ing in­spi­ra­tion from the re­gion of the chro­mo­some where these mol­e­cules re­side, she added; the num­ber 32 al­so is a shoutout to the im­por­tance of strat­e­gy, em­bod­ied by chess.

Michael Brox­son

The lead can­di­date blocks both C3 and C5 con­ver­tases, Holers said, play­ing in­to mul­ti­ple parts of the sys­tem. Their ini­tial fo­cus will be in kid­ney and skin dis­eases.

On top of the plat­form play, Q32 al­so in-li­censed an un­re­lat­ed an­ti­body that blocks IL-7 re­cep­tors from Bris­tol My­ers Squibb. The deal closed in Oc­to­ber, as Bris­tol My­ers Squibb was auc­tion­ing off as­sets on the back of its Cel­gene buy­out. At that point, it was al­so close to nom­i­nat­ing its first de­vel­op­ment can­di­date on the com­ple­ment side.

“In the spir­it of full trans­paren­cy,” CEO Mike Brox­son, a Take­da vet and for­mer chief of Goldfinch Bio who of­fi­cial­ly came on board in Feb­ru­ary, said, “but for Covid we might have launched the com­pa­ny sev­er­al months ago.”

While the com­pound, ADX-914, re­sides in the realm of adap­tive im­mu­ni­ty rather than in­nate im­mu­ni­ty where its tech plat­form op­er­ates, it pur­sues a sim­i­lar strat­e­gy not to com­plete­ly knock out a prob­lem­at­ic path­way but fine tune it. (Just don’t ex­pect any more such deals; af­ter this the 12-per­son team will fo­cus en­tire­ly on the com­ple­ment plat­form.)

“We’re re­al­ly about restor­ing home­osta­sis,” Brox­son said.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Francesco De Rubertis

Medicx­i's David Grainger and Francesco De Ru­ber­tis pump €200M in­to six com­pa­nies and what they say is a first-of-its kind fund

In what they’re billing as a first for biotech, David Grainger, Francesco De Rubertis and their team at Medicxi have put down €200 million to sweep up stakes in six companies from their predecessor VC and pump new money into them.

Medicxi didn’t disclose which companies it was investing in but the portfolio draws from Index Ventures Life VI, one of the last funds the Medicxi team launched while they were still part of the multinational, tech-focused VC firm Index Ventures. That team kept advising Index on their life sciences portfolio even after they spun out to form their own firm in the middle of 2016.

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President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.