Judith Shizuru (Stanford Department of Medicine via YouTube)

Jasper Ther­a­peu­tics launch­es out of Stan­ford with new ap­proach to stem cell treat­ment

The first girl in the tri­al came in with chron­ic di­ar­rhea and the im­mune sys­tem of an un­treat­ed HIV pa­tient. Born with a rare ge­net­ic dis­ease that im­ped­ed her abil­i­ty to make B and T cells, she had once been giv­en a stem cell trans­plant but it didn’t take.  Back in the hos­pi­tal, she was in­ject­ed with a new ex­per­i­men­tal an­ti­body and then giv­en a new stem cell trans­plant. Soon, she gained weight. The di­ar­rhea stopped.

“She has nor­mal T cells now,” Ju­dith Shizu­ru, the Stan­ford sci­en­tist who pi­o­neered the an­ti­body, told End­points News. “She’s in school.”

It’s the kind of med­ical sto­ry to launch a biotech around. To­day, Shizu­ru’s com­pa­ny Jasper Ther­a­peu­tics is emerg­ing out of stealth-mode with $35 mil­lion in Se­ries A fund­ing led by Abing­worth and Qim­ing, a mol­e­cule from Am­gen, and a Phase I tri­al set for its first read­out on Mon­day at ASH.

Jasper is broad­ly aimed at mak­ing stem cell trans­plants safer, more ac­ces­si­ble and more ef­fec­tive by us­ing an­ti­bod­ies as con­di­tion­ing agents. These agents clear out bone mar­row to make room for the new stem cells to graft on­to the body.

The new com­pa­ny is one of a hand­ful now us­ing an­ti­bod­ies to help ease stem cell trans­plan­ta­tion. Cal­i­for­nia-based Forty Sev­en is test­ing a com­bi­na­tion of two an­ti­bod­ies, a c-Kit and a CD-47, in mon­keys. In Cam­bridge, Mass., Ma­gen­ta Ther­a­peu­tics is work­ing on a c-Kit that re­leas­es a tox­in af­ter it binds.

William Lis

Jasper’s Phase I us­es a naked an­ti­body called JSP191 to help pa­tients with se­vere com­bined au­toim­mune de­fi­cien­cy re­ceive stem cell trans­plants – the on­ly pos­si­ble cure for the life-threat­en­ing dis­ease – but such trans­plants are used in a wide va­ri­ety of con­di­tions and Jasper has broad­er aims. Those in­clude oth­er au­toim­mune dis­eases, acute myeloid leukemia and cell-di­rect­ed gene ther­a­py.

“There’s a sig­nif­i­cant amount of progress be­ing made in gene ther­a­py,” in­ter­im CEO William Lis told End­points, “but no progress be­ing made in a con­di­tion­ing agent that will help graft gene ther­a­py.”

Shizu­ru path to the new an­ti­body was long and for­tu­itous. In 1987, Arl Arzst, the leg­endary ad ex­ec­u­tive and pres­i­dent of Proc­tor and Gam­ble in­ter­na­tion­al flew in on a re­cruit­ing trip for Stan­ford busi­ness stu­dents. There he vis­it­ed Shizu­ru, a young bi­ol­o­gy PhD can­di­date, be­cause he knew her room­mate. Arzst’s daugh­ter had di­a­betes and as Shizu­ru ex­plained the work she was do­ing on pan­cre­at­ic islet cell trans­plants, he told her to come to Eu­rope.

Shizu­ru had nev­er been to Eu­rope, but there Ar­szt in­tro­duced her to Ken Far­ber and the oth­er founders of the Ju­ve­nile Di­a­betes Foun­da­tion (now the JDRF). The founders struck a years-long cor­re­spon­dence and en­cour­aged Shizu­ru to go to med­ical school, where she de­cid­ed that if sci­en­tists were ever go­ing to de­vel­op trans­plants that didn’t trig­ger an im­mune re­sponse, it would be through stem cell work. She con­tin­ued her work at the Irv Weiss­man’s Stan­ford re­gen­er­a­tive lab, where even­tu­al­ly a grad­u­ate stu­dent made a dis­cov­ery that piqued her in­ter­est.

To put new stem cells in, you have to get the old stem cells out. That’s not al­ways easy. The cells sit in these pock­ets in the bone mar­row, and they’re pret­ty com­fort­able there. Doc­tors have to force them out, of­ten us­ing chemother­a­py or ra­di­a­tion, which dam­age DNA and cause se­vere side ef­fects. The costs some­times out­weigh the ben­e­fits.

“There are dis­eases we’re not treat­ing be­cause it’s too dan­ger­ous,” Shizu­ru said. “And the kids we’re treat­ing, they’re so, so frag­ile.”

The grad stu­dent had shown in mice that an­ti­bod­ies could be used to de­plete the stem cells and po­ten­tial­ly elim­i­nate the need for chemother­a­py or ra­di­a­tion. Shizu­ru and her team be­gan look­ing to see if any­one had de­vel­oped a hu­man ver­sion of the an­ti­body, CD117. It turned out Am­gen had al­ready de­vel­oped a ver­sion of this an­ti­body for a dif­fer­ent use. It al­so turned out she had a for­mer post­doc and a for­mer ad­vi­sor who worked there. They be­gan a col­lab­o­ra­tion.

“We set out to cross the val­ley of death,” Shizu­ru said, us­ing an in­dus­try slang term for the jump from an­i­mal mod­els to hu­man us­es.

Af­ter mak­ing a va­ri­ety of tweaks to the treat­ment, they pub­lished a pa­per in Sci­ence Trans­la­tion­al Med­i­cine in 2016 show­ing the an­ti­bod­ies cre­at­ed a 10,000 fold re­duc­tion in the num­ber of stem cells in mice.

The same year, they be­gan a clin­i­cal tri­al on 90 SCID pa­tients. These pa­tients had re­ceived stem cell trans­plants when they were very young but hadn’t been giv­en chemo or ra­di­a­tion for fear the side ef­fects would be too se­vere. The orig­i­nal trans­plants boost­ed their num­ber of im­mune cells, but with­out chemo or ra­di­a­tion, the stem cells don’t graft in­to those pock­ets and the body won’t con­tin­ue pro­duc­ing T cells. With­out those, they are ex­tra­or­di­nar­i­ly prone to in­fec­tion. Many pass away be­fore age 2.

The hope is that the an­ti­bod­ies al­lowed the stem cells to graft, and the pre­lim­i­nary an­swer to that ques­tion will be out on Mon­day. For the first girl in the tri­al, life has im­proved but ques­tions about how long her body will make im­mune cells re­main. Still, for that girl and oth­ers, Shizu­ru is con­fi­dent.

“We see there is stem cell en­graft­ment,” Shur­izi said. “They are ac­tu­al­ly mak­ing new T cells.”

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.