Nancy Yu (RDMD)

Abun­dant fund­ing, sparse da­ta: San Fran­cis­co start­up backs 're­al world' mod­el for rare dis­ease drug de­vel­op­ment

Rare dis­eases, a field of drug de­vel­op­ment where fund­ing far out­strips re­search on of­ten poor­ly un­der­stood con­di­tions, can leave sci­en­tists of­ten rein­vent­ing the wheel to en­gi­neer ther­a­peu­tics.

RD­MD, a San Fran­cis­co-based com­pa­ny, has a plan to ad­dress that im­passe by serv­ing as a con­duit be­tween the pa­tient and the drug de­vel­op­er. The plat­form courts pa­tients with rare dis­eases by help­ing them ac­cess med­ical records and par­tic­i­pate in re­search, while for drug de­vel­op­ers, the com­pa­ny struc­tures the com­piled da­ta in an ef­fort to build re­search pro­grams and de­vel­op an ev­i­dence base palat­able for reg­u­la­to­ry au­thor­i­ties.

Un­til now, com­pa­nies big and small in the space have been stuck look­ing for pa­tients in 10, 20 or more hos­pi­tals, de­pend­ing on the dis­ease, not­ed co-founder Nan­cy Yu in an in­ter­view.

“So most com­pa­nies are grow­ing their in­ter­nal teams, as well as work­ing with con­tract re­search or­ga­ni­za­tions, and sub­con­tract­ing to up to some­times 15 dif­fer­ent soft­ware ven­dors to man­age the process,” Yu said.

Stream­lin­ing this process, and help­ing pa­tients them­selves ac­cess their da­ta and par­tic­i­pate in re­search, could change the way the rare dis­ease drug de­vel­op­ment is con­duct­ed, RD­MD hopes. This lofty goal was giv­en a $14 mil­lion in­jec­tion on Thurs­day in a Se­ries A round led by Spark Cap­i­tal, a ven­ture cap­i­tal firm that has pre­vi­ous­ly backed com­pa­nies such as Slack, Twit­ter and Ocu­lus.

“At the end of the day, rare dis­ease just re­quires a dif­fer­ent mod­el for drug de­vel­op­ment,” Yu said. “The chal­lenge is re­al­ly un­der­stand­ing what the dis­ease ac­tu­al­ly is and how you can best cre­ate and de­sign a pro­gram around ev­i­dence that ex­ists. It’s re­al­ly hard to de­sign a suc­cess­ful pro­gram if you don’t know much about the dis­ease.”

That re­quires pa­tient da­ta which, apart from be­ing scarce, are not all ac­ces­si­ble in one uni­ver­sal elec­tron­ic med­ical records sys­tem.

“So we get per­mis­sion from pa­tients … to be able to get all their records from their var­i­ous fa­cil­i­ties. And that’s both be­cause we want to em­pow­er pa­tients with that choice of opt­ing in to par­tic­i­pate in re­search, but it’s al­so a ne­ces­si­ty op­er­a­tional­ly for us to be able to get that in­for­ma­tion, be­cause it doesn’t sit in a cen­tral data­base some­where,” she said.

With the pa­tient’s con­sent, the da­ta are then col­lat­ed and dis­sem­i­nat­ed to com­pa­nies to give them a com­pre­hen­sive un­der­stand­ing of the dis­ease, and con­se­quent­ly, de­sign clin­i­cal tri­als, de­ter­mine what end­points and bio­mark­ers are rel­e­vant, and even ed­u­cate pay­ers and in­sur­ance com­pa­nies so they can cov­er the drugs up­on ap­proval.

There’s a lot that pa­tients can con­tribute to in terms of re­search that doesn’t nec­es­sar­i­ly in­volve par­tic­i­pat­ing in a clin­i­cal tri­al, she added.

“For ex­am­ple, some of this da­ta could be used to sup­port and elim­i­nate the need for a place­bo con­trol arm be­cause you’re just look­ing at da­ta that al­ready ex­ists in the re­al world around pa­tients and their nat­ur­al pro­gres­sion of dis­ease,” Yu said. “And so that’s cer­tain­ly some­thing that every­one is very fo­cused on and hop­ing to use the da­ta for.”

Sound fa­mil­iar? A New York-based tech com­pa­ny called Flat­iron Health that was swal­lowed by Swiss gi­ant Roche in 2018, has sim­i­lar plans to use re­al-world ev­i­dence to re­place more tra­di­tion­al clin­i­cal tri­al da­ta to help the FDA make de­ci­sions for can­cer drugs.

But tra­di­tion­al ran­dom­ized con­trolled tri­als (RCTs) are con­sid­ered the gold stan­dard to prove if a com­pound or in­ter­ven­tion is safe and ef­fec­tive for its in­tend­ed use — they are used to show that a ben­e­fit or ad­verse event ob­served is not a mat­ter of chance or bias.

But giv­en lim­i­ta­tions such as strict in­clu­sion cri­te­ria, which typ­i­cal­ly dis­qual­i­fy old­er pa­tients and those suf­fer­ing from co-mor­bidi­ties, RCTs can be an in­ac­cu­rate rep­re­sen­ta­tion of pa­tients in the re­al world. But skep­tics crit­i­cize that re­ly­ing sole­ly on re­al-world ev­i­dence could be dan­ger­ous, as the process has the po­ten­tial to in­tro­duce re­searcher bi­as­es, and is not sub­ject to the same method­olog­i­cal rig­or.

That be­ing said, un­like can­cer drug de­vel­op­ment, rare dis­ease tri­als are of­ten ham­pered by slow en­roll­ment due to the scarci­ty of pa­tients — and the FDA re­quires a much small­er body of ev­i­dence for de­ci­sion mak­ing. Sarep­ta Ther­a­peu­tics’ pi­o­neer­ing Duchenne mus­cu­lar dy­s­tro­phy (DMD) drug Ex­ondys 51, for in­stance, was ap­proved on the ba­sis of a tiny non-place­bo con­trolled tri­al that com­pared the ef­fect of the drug to the nat­ur­al course of the dis­ease.

De­spite stiff op­po­si­tion from with­in and out­side the agency from crit­ics who said da­ta were in­suf­fi­cient to war­rant ap­proval, the FDA cleared the drug for use in a sub­set of pa­tients with the rare mus­cle-wast­ing dis­ease in 2016, prompt­ing some to sug­gest the agency had bowed to pres­sure from pa­tient ad­vo­cates. On­ly in 2019 did Sarep­ta sub­mit plans for a con­fir­ma­to­ry tri­al, which is ex­pect­ed to be com­plet­ed by 2024. But in the mean­time, the com­pa­ny has since se­cured an­oth­er DMD ap­proval on the ba­sis of a 24 pa­tient study.

Yu, who pre­vi­ous­ly worked with con­sumer ge­net­ics com­pa­ny 23andme, set up RD­MD in late 2017 soon af­ter co-founder On­no Faber was di­ag­nosed with a rare ge­net­ic dis­ease called NF2 (Neu­rofi­bro­mato­sis Type 2), which af­fects 1 in 30,000 peo­ple.

“And so when we got to­geth­er, it was re­al­ly to fig­ure out how do we tack­le this — there are 7000 con­di­tions and like one in 10 peo­ple have a rare dis­ease that in ag­gre­gate, it’s a re­al­ly big prob­lem,” she not­ed.

On Thurs­day, the com­pa­ny al­so un­veiled a part­ner­ship with Bel­gium-based drug­mak­er UCB for up to five years to work on pro­gres­sive supranu­clear pal­sy (PSP), a rare neu­rode­gen­er­a­tive dis­ease.

In ad­di­tion, RD­MD is al­so part­ner­ing with pa­tient ad­vo­ca­cy or­ga­ni­za­tions and physi­cian con­sor­tiums across 12 con­di­tions, in­clud­ing the Chil­dren’s Tu­mor Foun­da­tion, Cure San­fil­ip­po Foun­da­tion and Na­tion­al Tay-Sachs & Al­lied Dis­eases As­so­ci­a­tion.

The Se­ries A round al­so in­clud­ed the par­tic­i­pa­tion of ex­ist­ing seed in­vestors Lux Cap­i­tal, Vil­lage Glob­al and Garu­da Ven­tures, and new in­vestor Maveron. The mon­ey will be used, among oth­er things, to ex­pand in­to a fur­ther 20 rare con­di­tions and en­sure the con­ti­nu­ity of re­search pro­grams through­out the Covid-19 pan­dem­ic.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

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