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.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.