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.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.

Kristin Fortney, BioAge Labs CEO

An­ti-ag­ing biotech up­start plucks a drug from Am­gen's dis­card pile, piv­ot­ing from heart fail­ure to mus­cle con­di­tions

Back in April 2019, Amgen quietly shut down a Phase I trial for a drug named AMG 986. There was no safety concern; the molecule just didn’t hit the mark on helping the small band of heart failure patients who received it.

A small biotech, though, believes it would stand a chance in the burgeoning anti-aging field.

BioAge Labs has licensed AMG 986 — now renamed BGE-105 — with plans to parlay the existing IND into a quick Phase I trial teasing out the pharmacodynamic effects and set the stage for mid-stage tests focused on acute muscle indications.

Stéphane Bancel, Moderna CEO (Jeff Rumans)

'Learned a lot last year': Af­ter Covid-19 suc­cess, Mod­er­na's Stéphane Ban­cel plans to give rest of pipeline a big push

A year ago, Stéphane Bancel would have described Moderna as cautious — walking step-by-step to investigate whether mRNA vaccines could prevent a host of viruses. Then the pandemic hit, and the Cambridge, MA-based biotech got a multibillion-dollar windfall to produce the world’s second-ever authorized mRNA vaccine in a matter of months.

What’s next? Bancel is planning a big acceleration and expansion of the rest of the pipeline, including the company’s Phase III-ready candidate for cytomegalovirus (CMV), which was the lead program before Covid-19 came around.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.