CEO Jason Coloma (Maze)

Ex­clu­sive: Maze un­veils their $191M pipeline, tak­ing on Ver­tex and two long-sought con­di­tions

More than two years af­ter emerg­ing from stealth mode with $191 mil­lion, a guild of pres­ti­gious sci­en­tif­ic founders and sup­port from some top-flight VCs, Maze Ther­a­peu­tics is fi­nal­ly ready to un­veil what they’ve been up to.

Maze CEO Ja­son Colo­ma walked End­points News through their de-stealthed pipeline Mon­day, show­cas­ing three pro­grams that are still ear­ly stage but pro­gressed since the com­pa­ny’s 2019 launch. They in­clude a new small mol­e­cule ap­proach for the rare lyso­so­mal dis­or­der Pompe dis­ease, a chron­ic kid­ney dis­ease tar­get that will put them in square com­pe­ti­tion with Ver­tex, and an ALS gene ther­a­py that the­o­ret­i­cal­ly could be mar­ket­ed for the en­tire pa­tient pop­u­la­tion.

The tar­gets all come from the ini­tial batch of pro­grams the Maze’s founders seed­ed the com­pa­ny with at the start, but they al­so an­nounced new di­rec­tions for their ear­li­er stage re­search, with plans to broad­ly fo­cus on car­dio/re­nal, car­dio­vas­cu­lar, neu­rol­o­gy, eye and meta­bol­ic dis­eases and use a num­ber of tech­nolo­gies. Even­tu­al­ly, that could give them 10 to 15 pro­grams be­tween them­selves and their part­ners.

To plan for that ex­pan­sion, they’ve hired At­ul Dan­dekar, who led oph­thal­mol­o­gy at Roche and Genen­tech, as chief strat­e­gy of­fi­cer.

“In or­der to ex­e­cute on that strat­e­gy, of course, it’s not triv­ial,” Colo­ma said of the 10-15 pro­gram plan. “For a small com­pa­ny to try to be in­di­ca­tion ag­nos­tic and modal­i­ty ag­nos­tic, how do you make those trade-offs be­tween dif­fer­ent lev­els of in­vest­ments? And to have some­one who has seen pro­grams not on­ly get in­to the clin­ic but in­to the mar­ket­place I think is im­por­tant.”

Al­though Maze launched with a stat­ed goal of find­ing new so-called ge­net­ic mod­i­fiers — un­der­ap­pre­ci­at­ed genes that can change the sever­i­ty of a mono­genet­ic dis­ease like sick­le cell — all of the com­pa­ny’s ini­tial pro­grams go af­ter genes that have been stud­ied pre­vi­ous­ly, in­clud­ing, in one case, to the ex­tent that a ri­val com­pa­ny put a drug for it in Phase II last year. But Colo­ma said that each re­lies on tech­niques Maze col­lect­ed and de­vel­oped to turn those genes in­to drugs.

“Some of these tar­gets have been known for a while,” he said. “But it took many, many years to fig­ure out how do we uti­lize all the dif­fer­ent tech­nolo­gies at our dis­pos­al to ac­tu­al­ly turn that in­to a drug­ging pro­gram.”

The Pompe dis­ease pro­gram, for in­stance, goes af­ter a gene called Gys1 that is re­spon­si­ble for mak­ing glyco­gen in cells. The rare mus­cle-wast­ing con­di­tion aris­es when glyco­gen builds up in the cells of pa­tients who don’t have a func­tion­ing copy of the en­zyme for dis­pos­ing the sug­ary mol­e­cule, and drug pro­grams have large­ly ei­ther in­fused ar­ti­fi­cial copies of that en­zyme or sought to de­liv­er a gene for a healthy one. For years, though, re­searchers the­o­rized you could al­so in­hib­it Gys1 and pre­vent glyco­gen from build­ing up in the first place.

Maze fig­ured out two pieces of the puz­zle to make such a pro­gram pos­si­ble. First, Colo­ma claimed, Maze be­came the first com­pa­ny to crack the crys­tal struc­ture of the en­zyme Gys1 codes for. Sec­ond, he said, they used tis­sue and ge­net­ic da­ta from thou­sands of pa­tients at the UK biobank to find that peo­ple who hap­pen to have mu­tat­ed Gys1 genes func­tion­al nor­mal­ly, mean­ing that it should be safe to knock out.

Maze is now de­vel­op­ing a dai­ly pill for pa­tients with late-on­set stage of the dis­ease. It would be the first oral ther­a­py in a field dom­i­nat­ed by in­fused pro­teins and ex­per­i­men­tal gene ther­a­pies.

“That would be par­a­digm-chang­ing,” Colo­ma said.

The sec­ond pro­gram is for APOL1, a gene that has long been linked to a great­ly in­creased risk of kid­ney dis­ease. Ver­tex now has a mol­e­cule in Phase II for the APOL1-linked kid­ney con­di­tions. Colo­ma ar­gued that the com­pa­ny’s func­tion­al ge­nomics plat­form could give them new in­sights and give them a best-in-class drug, but he didn’t of­fer specifics on what those in­sights were or might be.

He not­ed that Ver­tex has yet to pub­lish their an­i­mal da­ta.

“I think you see that quite a bit in car­dio-re­nal,” Colo­ma said. “It’s not an area where you want to be nec­es­sar­i­ly first-in-class.”

Last­ly, they’ll de­vel­op a gene ther­a­py for ALS that tar­gets a gene called ATXN2. Biotechs de­vel­op­ing ALS gene ther­a­pies have un­der­stand­ably large­ly fo­cused on sin­gle genes that dri­ve ALS, but those genes on­ly ac­count for a small sub­set of pa­tients. De­vel­op­ing an ap­proach pi­o­neered by co-founder Aaron Gitler, Maze will look to knock out a gene whose ab­sence can help pro­tect against the buildup of dan­ger­ous plaques.

The first pro­gram, for pompe dis­ease, is slat­ed for the clin­ic in 2022.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Joan Butterton, Merck Research Laboratories VP of global clinical development, infectious diseases (Merck)

Mer­ck­'s ex­per­i­men­tal HIV drug is­la­travir hits with a PhI­II com­bo win and FDA fil­ing plans

Back in March, Merck and Gilead agreed to a partnership to challenge GlaxoSmithKline on long-acting HIV meds — by combining one drug from both Merck and Gilead that had shown potential. While Gilead brought its capsid inhibitor lenacapavir, Merck brought islatravir into the deal — a small molecule that the pharma acquired in 2012 from a small Japanese firm.

While that partnership is ongoing, islatravir is coming out of 2 Phase III pivotal trials with back-to-back successes and plans to beat a quick advance to the FDA.

Gil Beyen, Erytech CEO

A transat­lantic biotech flags a painful PhI­II can­cer flop, wav­ing a white flag

More than 4 years after little Erytech inflated some rare passion for its stock with upbeat Phase IIb data for their lead drug in pancreatic cancer, they’ve let the air out of the party balloons.

The transatlantic biotech $ERYP put the word out Monday morning that its drug eryaspase flopped in a Phase III pivotal for second line metastatic pancreatic cancer, slamming its stock, which plunged more than 30%.

Preston Klassen, Metacrine CEO

An­oth­er NASH play­er re­treats from bat­tered field af­ter tox­i­col­o­gy study flags po­ten­tial de­lay

NASH, the notorious liver disease afflicting an increasing number of Americans, has always been the focus at Metacrine ever since serial entrepreneur Rich Heyman unveiled the first round of financing all the way back in 2015.

Not anymore.

The San Diego-based biotech is halting its NASH program and choosing instead to prioritize its effort in pushing the same FXR agonist, MET642, into a Phase II trial for inflammatory bowel disease.