Jim Wilson (WuXi Global Forum at JPM20)

Mod­er­na sur­faces as the first part­ner for Jim Wilson's rare dis­ease non­prof­it, do­nat­ing an mR­NA pro­gram at no cost

A week af­ter Jim Wil­son and Alex Kar­nal de­buted their Tachi Ya­ma­da-in­spired non­prof­it aimed at treat­ing ul­tra-rare dis­eases, the part­ner pro­vid­ing the In­sti­tute for Life Chang­ing Med­i­cines with its first pipeline pro­gram has emerged from the shad­ows.

Alex Kar­nal

Mod­er­na jumped in­to the spot­light Tues­day, an­nounc­ing it had do­nat­ed an mR­NA-based ther­a­py for Crigler-Na­j­jar syn­drome free of charge. In a press re­lease, CEO Stéphane Ban­cel said Mod­er­na would have had to charge a for­tune if the com­pa­ny had gone on to de­vel­op it for prof­it giv­en the ul­tra-rare na­ture of the dis­ease.

But that’s ex­act­ly the kind of pro­gram IL­CM wants, Kar­nal told End­points News.

“They share our recog­ni­tion that there’s a mar­ket fail­ure in the for-prof­it world lead­ing to Crigler-Na­j­jar pa­tients be­ing left be­hind,” Kar­nal said of Mod­er­na. “It’s un­der­stand­able from an eco­nom­ic per­spec­tive for that to hap­pen … it speaks to the mar­ket to­day where these amaz­ing tech­nolo­gies are not read­i­ly avail­able for the peo­ple who need them.”

The can­di­date is called mR­NA-3351, and Wil­son says it orig­i­nal­ly emerged from a part­ner­ship he had with Alex­ion sev­er­al years ago. Alex­ion ul­ti­mate­ly ex­it­ed the mR­NA space and gave the full slate of pro­grams to Mod­er­na, with whom Wil­son con­tin­ued the col­lab­o­ra­tion.

What piqued Wil­son’s in­ter­est here was the use of an mR­NA ther­a­py in the event of an acute cri­sis. Crigler-Na­j­jar pa­tients tend to need about 12 hours of pho­tother­a­py every day,  large­ly char­ac­ter­ized by sleep­ing un­der bright blue lights, in or­der not to de­vel­op jaun­dice. Some­times, if a pa­tient gets less of the ther­a­py than need­ed, emer­gency in­ter­ven­tion may be need­ed.

The In­sti­tute’s new pro­gram can step in here, Wil­son says, as one po­ten­tial ap­pli­ca­tion could be to stock phar­ma­cies with an ap­proved drug, al­low­ing pa­tients to re­ceive treat­ment should the need arise. If pa­tients al­so need to trav­el long dis­tances on a plane, or through an­oth­er method where bring­ing along their pho­tother­a­py beds is cum­ber­some, they can head to the phar­ma­cy ahead of time and not have to wor­ry about their dis­ease.

“This would be in the phar­ma­cy of hos­pi­tals or avail­able quick­ly in stores, and if a pa­tient gets in trou­ble or re­quires a ma­jor surgery or needs to trav­el, they get their in­fu­sion and they would then be main­tained on their stan­dard of care, which is blue lights,” Wil­son said.

The oth­er use Wil­son en­vi­sions for the drug is as a main­te­nance ther­a­py, re­plac­ing the blue lights al­to­geth­er. Da­ta from the pro­gram have shown in mouse mod­els the ther­a­py could prove ef­fec­tive for al­most three weeks, he said, pos­si­bly al­low­ing pa­tients to vis­it a clin­ic at about the same rate.

Kar­nal al­so shed some more light on the pri­or­i­ty re­view vouch­er sys­tem the In­sti­tute will uti­lize to bring in funds. The non­prof­it plans on rais­ing mon­ey to de­vel­op the Crigler-Na­j­jar pro­gram sole­ly through phil­an­thropic do­na­tions, and be­cause the can­di­date has re­ceived the FDA’s rare pe­di­atric dis­ease des­ig­na­tion, Mod­er­na and the In­sti­tute are el­i­gi­ble to re­ceive a vouch­er should it be ap­proved.

Whether or not Mod­er­na de­cides to use or pass on the vouch­er, the In­sti­tute will re­ceive funds tied to the val­ue of the PRV or its proxy, which will then be used to bring in more pipeline pro­grams el­i­gi­ble for the same des­ig­na­tion as the Crigler-Na­j­jar treat­ment. Once the In­sti­tute has seen mul­ti­ple ap­provals, it will start sell­ing con­tracts tied to the vouch­ers to con­tin­ue bring­ing in more pro­grams, Kar­nal said, cre­at­ing a cy­cle of “self-sus­tain­ing in­de­pen­dence.”

Ul­ti­mate­ly, Kar­nal and Wil­son are hope­ful the Crigler-Na­j­jar pro­gram is just the start of things to come. Wil­son has re­searched this spe­cif­ic dis­ease for a while and be­lieves the tri­al de­sign can win over reg­u­la­tors by us­ing biliru­bin — the com­pound im­pli­cat­ed in jaun­dice — as a bio­mark­er.

“We think there’s a good chance we could get the prod­uct reg­is­tered by demon­strat­ing a de­crease in biliru­bin with­out the need for clin­i­cal end­points, as it’s as close to a val­i­dat­ed clin­i­cal bio­mark­er as cho­les­terol would be for fa­mil­ial hy­per­c­ho­les­terolemia be­cause it’s biliru­bin that ac­tu­al­ly caus­es the tox­i­c­i­ty in the brain,” Wil­son said.

“We are poised to be­gin tox­i­col­o­gy stud­ies and sub­mit brief­ing docs as we speak,” he added.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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