Erik van den Berg, AM-Pharma CEO

Years af­ter Pfiz­er passed on a buy­out op­tion, AM-Phar­ma finds a new part­ner for its kid­ney drug

A cou­ple of years ago, Pfiz­er passed on an op­tion to buy out AM-Phar­ma and its re­com­bi­nant hu­man al­ka­line phos­phatase for kid­ney fail­ure on the heels of some mixed Phase II da­ta. Now, the pro­gram has at­tract­ed a new part­ner — and an ap­proval could mean a big pay­out for AM-Phar­ma.

Tokyo-based Ky­owa Kirin is putting down $23.6 mil­lion up­front for ex­clu­sive de­vel­op­ment and com­mer­cial­iza­tion rights to ilo­fo­tase al­fa in Japan. There’s an­oth­er $148 mil­lion in biobucks on the line, adding up to a $290 mil­lion deal with “tiered dou­ble-dig­it roy­al­ties” and a drug sup­ply fee.

AM-Phar­ma will be re­spon­si­ble for an on­go­ing Phase III study, which seeks to en­roll up to 1,600 pa­tients with sep­sis-as­so­ci­at­ed acute kid­ney in­jury and is ex­pect­ed to pro­duce da­ta in 2023. The com­pa­ny’s al­so on the hook for a Phase I PK, safe­ty and tol­er­a­bil­i­ty study in Japan. Af­ter that, Ky­owa Kirin will take the can­di­date to reg­u­la­tors.

Sep­sis is a life-threat­en­ing or­gan dys­func­tion that’s caused by an im­prop­er host re­sponse to in­fec­tion. The kid­ney is the most com­mon­ly af­fect­ed or­gan, re­sult­ing in AKI, which oc­curs in 40% to 60% of crit­i­cal-care ad­mis­sions, ac­cord­ing to the part­ners.

Ilo­fo­tase al­fa works by de­phos­pho­ry­lat­ing sub­stances that can trig­ger the im­mune sys­tem in­to dev­as­tat­ing the kid­ney, thus detox­i­fy­ing them and re­duc­ing the in­flam­ma­tion. In a Phase II tri­al, a 1.6 mg/kg dose showed a 46% rel­a­tive re­duc­tion in mor­tal­i­ty com­pared to the place­bo group (p=0.022). How­ev­er, the drug missed its pri­ma­ry end­point of im­prov­ing kid­ney func­tion in sev­en days.

“Short term kid­ney func­tion im­prove­ment was re­al­ly more a de­sign for the Phase II study to be able to pick the most op­ti­mal dose,” CEO Erik van den Berg told End­points News back in 2019. “It’s kind of a bio­mark­er if you like. For Phase III one has to choose hard clin­i­cal end­points, and the most pre­ferred end­point by the reg­u­la­tors is the mor­tal­i­ty in this set­ting.”

Pfiz­er had paid $87.5 mil­lion for a mi­nor­i­ty stake in AM-Phar­ma and an ex­clu­sive op­tion to buy out the rest of the com­pa­ny back in 2015. The phar­ma walked away from the deal fol­low­ing the Phase II read­out, cit­ing “in­ter­nal strate­gic rea­sons.” But AM-Phar­ma pushed on with a Phase III tri­al any­way, en­rolling the first pa­tient in its piv­otal RE­VIVAL study back in No­vem­ber. The tri­al was planned with the help of a small boost from Cowen Health­care In­vest­ments and a loan from the Eu­ro­pean In­vest­ment Bank last March.

“Based on the num­ber of suc­cess­ful in­ter­na­tion­al part­ner­ships they have, they are the ide­al part­ner to sup­port the com­mer­cial­iza­tion of ilo­fo­tase al­fa in Japan,” van den Berg said of Ky­owa Kirin in a state­ment.

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?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.

UCB buys its way to epilep­sy show­down with Jazz with $1.9B Zo­genix ac­qui­si­tion

Zogenix’s epilepsy drug Fintepla may only have brought in around $100 million of sales in its first year, but UCB clearly believes it can go much, much higher.

The Belgian pharma has inked a $1.9 billion deal to buy out Zogenix, paying $26 per share in cash and offering a contingent value right worth $2 more per share if Fintepla lands an extra EU approval by the end of 2023.

But even the upfront marks a 72% premium to California-based Zogenix’s shares, which were trading just north of $15 on Tuesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,300+ biopharma pros reading Endpoints daily — and it's free.