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 in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Eli Lil­ly and Te­va pre­pare for court bat­tle over mi­graine med ri­val­ry

It looks like Eli Lilly and Teva Pharmaceuticals are going to trial.

A federal appeals court on Monday refused to invalidate three of Teva’s patents for its migraine treatment Ajovy, while also declining to issue a summary judgment in favor of either company, which would effectively end the case without a full trial.

Teva filed suit against Lilly back in 2018, alleging that the company infringed upon nine patents with its rival migraine drug Emgality. The rival drugs were both approved in September 2018 for the preventative treatment of migraine, and are designed to block calcitonin gene-related peptide (CGRP), a protein associated with the onset of migraine pain.

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Rep. Vern Buchanan (R-FL) (Bill Clark/CQ Roll Call via AP Images)

Af­ter cov­er­age re­stric­tions for Alzheimer's drugs, bi­par­ti­san House bill would force CMS to re­view drugs in­di­vid­u­al­ly

When Biogen’s controversial Alzheimer’s drug Aduhelm was hit with a national decision from CMS that restricted coverage to only randomized trials, practically guaranteeing a commercial flop in the near term, questions surfaced over why CMS also included all amyloid-targeted monoclonal antibodies for Alzheimer’s disease.

With Eisai and Biogen’s second Alzheimer’s drug, lecanemab, now showing it can slow the rate of cognitive decline versus placebo, lining up for a likely full approval next spring, the question now turns to whether that data, which is being presented at the Clinical Trials on Alzheimer’s Congress in San Francisco in late November, will be enough for CMS when it asks, “Does the anti-amyloid mAb meaningfully improve health outcomes (i.e., slow the decline of cognition and function) for patients in broad community practice?”

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FDA+ roundup: Ad­comm date set for Cy­to­ki­net­ics heart drug; New gener­ic drug guid­ance to re­duce fa­cil­i­ty de­lays

The FDA on Wednesday set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, meaning regulators aren’t likely to meet the Nov. 30 PDUFA date that was previously set.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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