Tuyen Ong and Avak Kahvejian

One Ring to rule them all? Flag­ship’s big bet on dom­i­nat­ing gene ther­a­py 2.0 at­tracts a $117M megaround

Over the last 18 months or so, gene ther­a­py has come in for its come­up­pance.

Long known for once-and-done boast­ing, stak­ing claims for cu­ra­tive re­sults on some of the most bit­ter dis­eases known to man, the field has been stag­gered by fail­ure, ev­i­dence of wan­ing ef­fects and fears that ef­fi­ca­cy could wick­er and flame out. And giv­en the ther­a­pies’ vi­ral con­structs, they could on­ly be giv­en once.

As a re­sult, var­i­ous com­pa­nies have been work­ing on dif­fer­ent so­lu­tions. But at Flag­ship, which has been re­think­ing what think­ing big is, there’s one still quite stealthy ef­fort that aims to sweep aside the first gen­er­a­tion of ther­a­pies and sup­plant it with some­thing com­plete­ly new.

The biotech is Ring Ther­a­peu­tics, or­ga­nized around a cen­tral big plat­form idea: that a new kind of virus they’ve found — anellovirus­es — that typ­i­cal­ly live in har­mo­ny with your im­mune sys­tem, can be used in a va­ri­ety of tis­sues for a va­ri­ety of ther­a­peu­tic pur­pos­es. And, they hope, anellovirus­es can sim­ply re­place the still prob­lem­at­ic ade­n­ovirus­es that dom­i­nat­ed the first wave in this race, of­fer­ing a new fleet choice that can per­ma­nent­ly al­ter the field.

Like oth­er Flag­ship mod­els, the plat­form play here is based on lengthy lab work. Ring has been in busi­ness since 2017. And you don’t see any­one sweat­ing the fact that they’re on a hard march to their 5th an­niver­sary with no plans to be in the clin­ic any­time this year. At least, nei­ther the CEO-part­ner in­volved, Night­star vet­er­an Tuyen Ong, or Flag­ship’s Avak Kahve­jian sound con­cerned.

For them, this is a shot at the first true dis­rup­tion in gene ther­a­py in 50 years. They’re out to make biotech his­to­ry. Here’s the Flag­ship found­ing part­ner, Kahve­jian:

You know that Flag­ship doesn’t nec­es­sar­i­ly want to rush in­to the clin­ic with one pro­gram. We re­al­ly, tru­ly see this as a mul­ti­modal­i­ty, mul­ti­prod­uct plat­form. And as such, we want to stag­ger a num­ber of clin­i­cal en­tries to­geth­er with­in a rea­son­able time­frame where they’re over­lap­ping with each oth­er. So all of those pre­clin­i­cal stud­ies have to line up. And we want to demon­strate some of these re­al­ly in­ter­est­ing val­ue propo­si­tions. And pick­ing the right way to do that is go­ing to be im­por­tant.

There’s a pub­li­ca­tion com­ing soon that Kahve­jian is ex­cit­ed about. And Ong sounds hap­py to be in this spot, as they move in­to the IND stage.

I know you hear this prob­a­bly from a num­ber of dif­fer­ent biotechs, but I of­ten use the term, it’s a lit­tle bit corny, but it’s one Ring to rule them all. Be­cause when you look at gene ther­a­py, dif­fer­ent com­pa­nies are in­no­vat­ing on dif­fer­ent fronts. So there’s the cap­sid evo­lu­tion as you talked about, cap­sid en­gi­neer­ing, man­u­fac­tur­ing and the oth­er piece, which is the pay­loads. What Ring is do­ing is ac­tu­al­ly in­no­vat­ing on mul­ti­ple fronts. So we’ve tak­en these com­men­sal virus­es that are harm­less, they de­vel­oped spe­cif­ic ad­van­tages in terms of tro­pism, re­dos­abil­i­ty, po­ten­tial­ly be­ing more tol­er­a­ble and po­tent and we’ve been able to gen­er­ate a plat­form around that…

I think the prob­lem we have right now, John, is that we have an em­bar­rass­ment of rich­es in re­gards to which dis­eases to tar­get. I think how we’re look­ing at ba­si­cal­ly ad­dress­ing the clin­i­cal in­di­ca­tions is that one, you can have in­di­ca­tions that ad­dress both greater tol­er­a­bil­i­ty, which is an is­sue with­in the gene ther­a­py space, greater po­ten­cy, the abil­i­ty to ad­dress dif­fer­ent in­di­ca­tions that are not ad­dressed be­cause of lack of tro­pism. And then the fi­nal holy grail is to ad­dress the re­dos­abil­i­ty piece.

Ong had a front-row seat on just how ex­cit­ing, and fre­quent­ly dis­ap­point­ing, the first round of gene ther­a­pies has gone. He was head of de­vel­op­ment at Night­star un­til Bio­gen bought them out in the sum­mer of 2019. And both of Night­star’s main pro­grams just flamed out in the clin­ic, wip­ing out more than a half-bil­lion dol­lars in val­ue on Bio­gen’s books.

Ring’s sto­ry, mean­while, has at­tract­ed a much broad­er syn­di­cate to build on the Flag­ship launch round.

In­vus, Al­ti­tude Life Sci­ence Ven­tures, Part­ners In­vest­ment, UPMC En­ter­pris­es, as well as funds and ac­counts ad­vised by T. Rowe Price As­so­ci­ates, among oth­ers, joined in along­side Flag­ship Pi­o­neer­ing. They can count this as an­oth­er high-risk, high re­ward play in the Flag­ship port­fo­lio.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

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In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

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Ted Love, Global Blood Therapeutics CEO

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Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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HHS Secretary Xavier Becerra (Patrick Semansky/AP Images)

US weighs new route of ad­min­is­tra­tion for mon­key­pox vac­cine as cas­es climb — re­port

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When Kyle Planck first suspected he might have monkeypox in late June, he went to the CDC website and found six photos of different types of lesions. And that was about it for general public information.

Planck, who is a sixth-year PhD pharmacology researcher at Weill Cornell, kept looking though and found a separate part of the CDC website meant for healthcare professionals. There he found a medical slide deck with more pictures, professional journal articles and more details about symptoms and diagnosis.

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David Zaccardelli, Verona Pharma CEO

Verona’s COPD drug shines in PhI­II study, po­ten­tial­ly clear­ing path to FDA — shares jump

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John Oyler, BeiGene CEO (Paul Yeung/Bloomberg via Getty Images)

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BeiGene put out word Tuesday morning that a Phase III open-label global study, named RATIONALE 301, met its primary endpoint of non-inferior overall survival (OS) versus sorafenib as a first-line treatment in adults with unresectable hepatocellular carcinoma (HCC). The company claimed that the trial, which enrolled more than 600 patients from the US, Europe and Asia, showed a consistent safety profile from previous studies involving tislelizumab and reported no new safety signals.

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