Strate­gies for Biotechs Plan­ning FDA Ap­proval Path­ways in Cur­rent Fi­nan­cial Mar­ket

As the biotech fi­nan­cial mar­kets shift from a peak 12 months ago, even well-fund­ed biotechs are watch­ing pipeline burn rates as un­cer­tain­ty sur­rounds the next in­vest­ment rounds.

There is how­ev­er pos­i­tive news from the in­vest­ment sec­tor on fu­ture de­mand.  Ac­cord­ing to Fred Co­hen, co-founder, and chair­man of Mono­graph Cap­i­tal Part­ners in San Fran­cis­co “phar­ma has a tremen­dous need for new prod­ucts and it will on­ly ac­cel­er­ate over the next eight years”. But he said what in­vestors want is re­al in­no­va­tion, “not slight­ly bet­ter be­cause the pay­ers are not go­ing to pay you for just slight­ly bet­ter.”

Mean­while, in­dus­try ex­perts tapped by Novotech are point­ing to the Asia Pa­cif­ic for biotechs want­i­ng to con­serve funds while rapid­ly pro­gress­ing their clin­i­cal pro­grams, which al­so sup­ports in­vest­ment at­trac­tion for lat­er phase re­search.

Fred Co­hen, co-founder and chair­man of Mono­graph Cap­i­tal Part­ners


Fred Co­hen points to the ben­e­fits of hav­ing Asia Pa­cif­ic sites that of­fer vast pa­tient pop­u­la­tions.

“Frankly, there are dis­eases where it’s eas­i­er to re­cruit in Asia where those dis­eases are more preva­lent,” he said.

He said there are a num­ber of places where it makes sense to ex­tend your reach to re­cruit faster while you’re think­ing about op­ti­miz­ing spend. “What you are push­ing hard­est for is time to last pa­tient in.”

“The more you can short­en that, the more you can short­en the read­out on your tri­al, which is ul­ti­mate­ly what will be the fu­el that will dri­ve the sub­se­quent growth of your com­pa­ny.”

“Every­body tells you you had bet­ter cut your spend prob­a­bly by 10% or 15% and you had bet­ter fo­cus that spend
on your as­set that is far­thest along.”

“That is, you will fo­cus on your Phase II or your Phase Ib as­set and repri­or­i­tize pre­clin­i­cal work which is a po­lite way of say­ing, You’ll put it on the shelf un­til you can af­ford to do it.”

That dis­cus­sion is be­ing re­it­er­at­ed in board­room af­ter board­room af­ter board­room be­cause ul­ti­mate­ly what will make a biotech com­pa­ny suc­cess­ful is clin­i­cal da­ta in its lead as­set.

That’s where the val­ue gets cre­at­ed and every­one knows it.

Yi Lar­son, Lian­Bio chief fi­nan­cial of­fi­cer based in Shang­hai

Dis­cussing the ad­van­tages of a Chi­na pres­ence Yi Lar­son, the chief fi­nan­cial of­fi­cer of Lian­Bio based in Shang­hai, said that the founders Per­cep­tive Ad­vi­sors “saw a re­al need to build a new kind of com­pa­ny with the abil­i­ty to ac­cel­er­ate Chi­nese pa­tient ac­cess to in­no­v­a­tive new med­i­cines”.

Lian­Bio is a cross-bor­der biotech com­pa­ny with of­fices in Chi­na and the US fo­cussed on bring­ing in­no­v­a­tive drugs to Chi­na.

“What we’ve seen in re­cent years is new gov­ern­ment poli­cies that have been en­act­ed to im­prove health out­comes. Many of these poli­cies have re­al­ly helped the biotech ecosys­tem in Chi­na to flour­ish.”

“At Lian­Bio we in-li­cense med­i­cines unique­ly suit­ed to the Chi­nese mar­ket and have es­tab­lished a ro­bust clin­i­cal de­vel­op­ment, reg­u­la­to­ry, and med­ical af­fairs in­fra­struc­ture op­er­at­ing on the ground in Chi­na.”

Ad­dress­ing the cur­rent in­vest­ment mar­ket, she said “We’ve cer­tain­ly been very mind­ful of the cur­rent mar­ket con­di­tions and have been dis­ci­plined about our cash man­age­ment.”

“At the same time, we are for­tu­nate to be well-cap­i­tal­ized and in a po­si­tion to con­tin­ue to in­vest in our
pri­or­i­ty near-term com­mer­cial stage pro­grams and launch readi­ness ac­tiv­i­ties for these pro­grams.”

“I’ll say al­so that in this cur­rent en­vi­ron­ment, what we have seen is an uptick in in­ter­est from po­ten­tial west­ern biotech part­ners in pur­su­ing these re­gion­al deals.”

Jeanne No­vak, CEO, and pres­i­dent of CBR

Com­ment­ing on po­ten­tial lo­ca­tions for glob­al tri­als Jeanne No­vak, CEO, and pres­i­dent of CBR In­ter­na­tion­al in Boul­der, Col­orado said places like Aus­tralia of­fered sig­nif­i­cant op­por­tu­ni­ties, es­pe­cial­ly for ear­ly phase clin­i­cal stud­ies. The re­gion of­fers “in­cen­tives and the op­por­tu­ni­ty to get in­to re­al­ly high in­tegri­ty, very high-qual­i­ty Phase I op­por­tu­ni­ties”.

CBR In­ter­na­tion­al de­vel­ops glob­al clin­i­cal de­vel­op­ment plans for its US and Eu­ro­pean biotech client base.

“There is ab­solute­ly a shift in the de­vel­op­ment pat­terns that we’re see­ing in ear­ly clin­i­cal tri­als, and it is pri­mar­i­ly based on the avail­abil­i­ty and speed of ob­tain­ing op­por­tu­ni­ties to get in­to Phase I tri­als,” said Jeanne No­vak.

The shift that we’re see­ing is be­cause of many de­lays and some de­lays in tri­al start-up due to lim­it­ed ca­pac­i­ty and in­creased de­mand for CRO ser­vices. This is al­so true for get­ting in­to CRO’s Phase 1 units, et cetera here in the States; and even to some de­gree, in Eu­rope.

Aus­tralia, for ex­am­ple, has be­come much more of a tar­get for a lot of our ear­ly start­up com­pa­nies as well as young com­pa­nies that might be in­to their sec­ond or third prod­uct in their pipeline want­i­ng to get clin­i­cal da­ta ear­ly.

These clients are shift­ing their strate­gies for ear­ly de­vel­op­ment to places like Aus­tralia where the in­cen­tives and the op­por­tu­ni­ty to get in­to re­al­ly high in­tegri­ty, very high-qual­i­ty Phase I op­por­tu­ni­ties ex­ist. We are see­ing that shift.

Yi Lar­son said ex­pand­ing clin­i­cal tri­als to Chi­na is a re­al op­tion for biotechs want­i­ng to quick­ly re­cruit pa­tients.

She said while we’re not de­vel­op­ing for the US mar­ket, when work­ing with part­ners “we typ­i­cal­ly con­tribute any­where from 15% to 20% of the glob­al tri­al en­rol­ment from Chi­na as part of that glob­al tri­al, and we’ll lever­age that glob­al tri­al for ap­proval both in the US as well as in Chi­na”.

“Our core mod­el is to in-li­cense pro­grams for de­vel­op­ment in Chi­na and oth­er APAC re­gions.”

We like to bring in pro­grams that are at a stage where we can add val­ue to the glob­al pro­gram.

For ex­am­ple, by con­tribut­ing to Phase III tri­al en­roll­ment.

I can tell you that the abil­i­ty to con­tribute pa­tients to a glob­al pro­gram can be very mean­ing­ful to US-Eu­ro­pean-based part­ners.

Be­fore I was at Lian, I was the CFO of Turn­ing Point Ther­a­peu­tics where I led the out-li­cens­ing of Chi­na rights to our lead pro­grams.

The rea­son that we were in­ter­est­ed in a re­gion­al deal was be­cause of the clin­i­cal de­vel­op­ment re­sources, the part­ner was able to bring to the ta­ble and the abil­i­ty to quick­ly re­cruit pa­tients, par­tic­u­lar­ly in tri­als of pre­ci­sion med­i­cine can be very at­trac­tive.

An­oth­er way that we are max­i­miz­ing val­ue for clin­i­cal pro­grams is by pur­su­ing re­gion-spe­cif­ic in­di­ca­tion strate­gies.

For ex­am­ple, we’re study­ing our FGFR in­hibitor In­fi­gra­tinib, in gas­tric can­cer, which has a high­er preva­lence in Chi­na than in any oth­er ge­og­ra­phy.

In­di­ca­tion ex­pan­sion can gen­er­ate val­ue on a glob­al scale while al­so al­low­ing our part­ners con­serve their re­sources.


In terms of ac­cel­er­at­ed de­vel­op­ment path­ways in Chi­na there has been a lot of change ac­cord­ing to Yi. “Par­tic­u­lar­ly over the last few years that I think makes it such an ex­cit­ing place to be op­er­at­ing in biotech right now.”

“That comes in many forms. Reg­u­la­to­ry re­forms, we’ve seen Chi­na join­ing the ICH which has en­abled that abil­i­ty to join the glob­al clin­i­cal tri­als, al­so ac­cel­er­at­ed reg­u­la­to­ry path­ways, which in­clude pri­or­i­ty re­view, break­through ther­a­py des­ig­na­tion, and clin­i­cal tri­al waiv­er pro­grams, so mir­ror­ing a lot of the pro­grams that we al­ready have in the US as well as sig­nif­i­cant gov­ern­ment sup­port to re­al­ly fos­ter in­no­va­tion.”

That’s through their poli­cies, strate­gic in­vest­ments in the sec­tor, and sup­port­ing growth in the in­fra­struc­ture in Chi­na.

We’re al­so see­ing an im­proved re­im­burse­ment sys­tem through the na­tion­al re­im­burse­ment drug list, which now sees an­nu­al list­ing up­dates.

“It used to be much less fre­quent which are dri­ving more rapid and greater ac­cess through­out Chi­na as well as stronger IP pro­tec­tion. All of those things, I think, are mak­ing it a much more fa­vor­able en­vi­ron­ment to be op­er­at­ing in and al­so much more aligned with the glob­al de­vel­op­ment.”


Yi al­so com­ment­ed on the FDA ap­proval process around mul­ti-cen­ter tri­als.

“The FDA has ac­tu­al­ly been very clear about their re­quire­ments to get FDA ap­provals.”

“They’re look­ing for mul­ti-cen­ter ran­dom­ized con­trol clin­i­cal tri­als which demon­strate ap­plic­a­bil­i­ty to the pa­tient pop­u­la­tion in the US.”

“They al­so want to make sure that pri­ma­ry end­points are ap­plic­a­ble to the stan­dard of care in the US and that the con­trol arm is al­so ap­plic­a­ble to stan­dard of care in the US. These are all in­cred­i­bly im­por­tant.”

Jeanne No­vak agreed say­ing “The FDA is ac­tu­al­ly very open to clin­i­cal da­ta com­ing from out­side of the US”.

“With re­gards to, again, Phase I stud­ies that are de­signed and con­duct­ed in Aus­tralia, for ex­am­ple, it’s known that of­ten­times the da­ta and the safe­ty da­ta col­lec­tion and mon­i­tor­ing is, again, of such a high qual­i­ty that these da­ta are read­i­ly ac­cept­ed by the FDA.”

“Cer­tain­ly, if the study is de­signed ap­pro­pri­ate­ly, these re­sults can ab­solute­ly spring­board a pro­gram di­rect­ly in­to a Phase II or maybe a Phase Ib with an ex­pand­ed op­por­tu­ni­ty to con­tin­ue eval­u­at­ing dos­ing and sched­ule.”

“Of­ten­times, we ad­vise that if it’s pos­si­ble to get ear­ly clin­i­cal da­ta in a Phase I, nor­mal healthy vol­un­teers again, in Aus­tralia, that of­ten­times it can be very im­por­tant in­for­ma­tion for fil­ing even an ear­ly ap­pli­ca­tion with the FDA; or can serve to sup­port a re­quest for a meet­ing to ac­tu­al­ly dis­cuss the da­ta and not just bring it in to sup­port the Phase II. These da­ta can ac­tu­al­ly serve as a ba­sis for dis­cus­sions with FDA to help build a clin­i­cal de­vel­op­ment pro­gram with the FDA.”

I think a big­ger part of the ap­prov­abil­i­ty piece starts ear­ly in de­vel­op­ment. It is im­por­tant to be­gin ear­ly think­ing about how to try to es­tab­lish what are the bench­marks of safe­ty and the ef­fi­ca­cy end­points for a par­tic­u­lar prod­uct and clin­i­cal in­di­ca­tion. This is im­por­tant when de­sign­ing and ini­ti­at­ing ear­ly clin­i­cal stud­ies that can be de­signed to pro­vide mean­ing­ful ear­ly clin­i­cal sig­nals.

Al­so, ear­ly tri­als con­duct­ed out­side of the US can ad­dress some of the some of the key el­e­ments of phar­ma­co­ki­net­ics ear­ly be­fore we be­gin think­ing about Phase ll, lll and glob­al tri­als.

End­points that are in fact clin­i­cal­ly mean­ing­ful, which is a big top­ic with the FDA right now, not on­ly need to be sta­tis­ti­cal­ly sig­nif­i­cant but clin­i­cal­ly mean­ing­ful for the pop­u­la­tion that you in­tend to treat. These con­sid­er­a­tions can be pi­lot­ed in ear­ly stud­ies.

She said “build­ing those at­trib­ut­es and those con­sid­er­a­tions ear­ly in your tri­als and look­ing for those types of bench­marks and pay­ing at­ten­tion to not on­ly the de­sign and adding val­ue to the tri­al, but al­so the out­comes you’re look­ing for can ac­tu­al­ly guide that de­vel­op­ment pro­gram to­wards those piv­otal ef­fi­ca­cy stud­ies that can in fact re­sult in ap­proval in the US.


The need for ear­ly plan­ning and defin­ing a ro­bust pre­clin­i­cal pro­gram was al­so ad­dressed by Kasey Kime, the Di­rec­tor of Reg­u­la­to­ry Af­fairs at Novotech. She said there are 3 main points for biotechs to con­sid­er:

  1. The first is to know your prod­uct. Be­gin your prod­uct char­ac­ter­i­za­tion ear­ly, de­vel­op your tar­get prod­uct pro­file, and your as­so­ci­at­ed qual­i­ty tar­get prod­uct pro­file. This will help you un­cov­er chal­lenges to your de­vel­op­ment pro­gram.
  2. The next tip is to take ad­van­tage of all avail­able health au­thor­i­ty meet­ings.

Ed­u­cate your­self on which meet­ings you are el­i­gi­ble for and use this as an op­por­tu­ni­ty to dis­cuss those de­vel­op­men­tal chal­lenges.

This is go­ing to help you fo­cus your de­vel­op­ment and help save time and mon­ey and im­prove your over­all chances of fil­ing suc­cess.

  1. My third tip would be to think be­yond Phase I.

For ex­am­ple, if you are con­sid­er­ing ap­ply­ing for ac­cel­er­at­ed ap­proval, you need to con­sid­er the im­pact of that on your over­all de­vel­op­ment time­line be­cause of­ten the clin­i­cal de­vel­op­ment can move faster than the tra­di­tion­al CMC.

You need to give ear­ly con­sid­er­a­tion to ex­pe­dit­ing your CMC de­vel­op­ment if ac­cel­er­at­ed path­ways are part of your strat­e­gy.

In ad­di­tion, she said, Aus­tralia is an at­trac­tive ear­ly-phase des­ti­na­tion.

“Some of the well-known rea­sons for this are the rapid start-up time­lines,the over­all low­er cost of the tri­als due to the tax re­bate pro­gram, and the ef­fi­cien­cy of the reg­u­la­to­ry path­way.”

It’s quite a stream­lined reg­u­la­to­ry path­way un­der the CTN path­way and of course, the qual­i­ty of the clin­i­cal tri­al da­ta com­ing out of Aus­tralia.

“For those rea­sons, it is a very at­trac­tive place for ear­ly phase tri­als.”

She said in ad­di­tion, if a biotech has an open US IND, they are el­i­gi­ble for the CTN path­way in Aus­tralia.

She said that means some of the “bi­o­log­i­cals like the CART T ther­a­pies, if you have an open IND, you can dis­cuss with the TGA, and there is the abil­i­ty to stream­line that clin­i­cal tri­al un­der the CTN path­way.”

“Aus­tralia has a world-class health sys­tem and da­ta is ac­cept­ed by ma­jor reg­u­la­tors like the FDA and the EMA for fu­ture clin­i­cal tri­als.”


1. Fred Co­hen, co-founder and chair­man of Mono­graph Cap­i­tal Part­ners in San Fran­cis­co

“Think hard about your tar­get prod­uct pro­file and make sure that it will mat­ter.”

“Hav­ing thought about that, make sure that the clin­i­cal tri­al that you’re work­ing on ends up be­ing sup­port­ive of the di­rec­tion you’re head­ed in.”

2. Jeanne No­vak, the CEO and pres­i­dent of CBR In­ter­na­tion­al Corp in Boul­der, Col­orado

“Ab­solute­ly think about the long-term goals and be flex­i­ble as you are will­ing and able to col­lect clin­i­cal da­ta.”

“As­sess those da­ta ap­pro­pri­ate­ly and see if you’re still on tar­get for what your orig­i­nal plan might have been and make the ad­just­ments ear­ly so that you’re not falling so much in love with what your orig­i­nal the­o­ry might have been, but rather what the da­ta are telling you.”

“Quick­ly piv­ot if need­ed and con­tin­ue on a path to, again, de­vel­op­ing ex­cel­lent and high-in­tegri­ty clin­i­cal da­ta.”

3. Yi Lar­son, the chief fi­nan­cial of­fi­cer of Lian­Bio in Shang­hai

“I think as it re­lates to a glob­al de­vel­op­ment pro­gram, if you are think­ing about do­ing a re­gion­al or glob­al deal, the choice of part­ner re­al­ly mat­ters.”

“The deal it­self is just the be­gin­ning of a long-term re­la­tion­ship that re­quires very close col­lab­o­ra­tion in or­der
to re­al­ize the full val­ue of the deal which of­ten en­tails a great deal more work than most peo­ple ex­pect, so plan ahead, think about the tim­ing, and the choice of that part­ner. That re­al­ly mat­ters.”

4. Kasey Kime, the di­rec­tor of Reg­u­la­to­ry Af­fairs of Novotech

“I would say think care­ful­ly about your choice of CRO part­ner.”

“You want to pick a CRO with a proven track record and ex­pe­ri­enced staff in your ther­a­peu­tic area.”

Kasey Kime, the Di­rec­tor of Reg­u­la­to­ry Af­fairs at Novotech

BioDesk is Novotech’s in-house reg­u­la­to­ry con­sul­tan­cy group.

“We’re a lit­tle dif­fer­ent to oth­er reg­u­la­to­ry con­sul­tan­cy groups by the fact that we’re ac­tu­al­ly part of glob­al CRO Novotech that spe­cial­izes in biotech.”

Be­cause of that, we get to see a lot of in­no­v­a­tive prod­ucts and we get to work with a lot of dif­fer­ent glob­al health au­thor­i­ties, and we get to see how they treat these in­no­v­a­tive prod­ucts.

This kind of ex­pe­ri­ence is high­ly valu­able to our biotech clients, many of which are work­ing right at the cut­ting edge of sci­ence in ar­eas where the reg­u­la­to­ry guid­ance is lim­it­ed or not yet de­vel­oped.

“I would say our ma­jor strength at BioDesk is be­ing part of a glob­al CRO that spe­cial­izes in biotech.”

The Chi­na Biotech Land­scape – Op­por­tu­ni­ties in Chi­na and the Path to USF­DA Ap­proval” is avail­able to down­load here:­pers/chi­na-biotech-land­scape-op­por­tu­ni­ties-chi­na-and-path-usf­da-ap­proval