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.”

In a sec­ond big set­back for Covid-19 an­ti­body treat­ment hopes, Re­gen­eron halts en­roll­ment for more se­vere pa­tients

Regeneron has just delivered more bad news for the hope that neutralizing antibodies could be used to treat patients with more severe forms of Covid-19.

The New York biotech said today that an independent monitoring committee recommended halting enrollment of patients who need high-flow oxygen or mechanical ventilation in one of the trials on their antibody cocktail, after finding “a potential safety signal” and “an unfavorable risk/benefit profile.” The news comes a week after the NIH scrapped a trial of Eli Lilly’s Covid-19 antibody after finding it was having little effect on an initial cohort of hospitalized patients.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

Daphne Koller, Getty

Bris­tol My­er­s' Richard Har­g­reaves pays $70M to launch a neu­rode­gen­er­a­tion al­liance with a star play­er in the ma­chine learn­ing world

Bristol Myers Squibb is turning to one of the star upstarts in the machine learning world to go back to the drawing board and come up with the disease models needed to find drugs that can work against two of the toughest targets in the neuro world.

Daphne Koller’s well-funded insitro is getting $70 million in cash and near-term milestones to use their machine learning platform to create induced pluripotent stem cell-derived disease models for ALS and frontotemporal dementia.

Patrick Soon-Shiong at the JP Morgan Healthcare Conference, Jan. 13, 2020 (David Paul Morris/Bloomberg via Getty Images)

Af­ter falling be­hind the lead­ers, dissed by some ex­perts, biotech show­man Patrick Soon-Sh­iong fi­nal­ly gets his Covid-19 vac­cine ready for a tri­al. But can it live up to the hype?

In January, when dozens of scientists rushed to start making a vaccine for the then-novel coronavirus, they were joined by an unlikely compatriot: Patrick Soon-Shiong, the billionaire doctor most famous for making big, controversial promises on cancer research.

Soon-Shiong had spent the last 4 years on his “Cancer Moonshot,” but part of his project meant buying a small Seattle biotech that specialized in making common-cold vectors, called adenoviruses, to train the immune system. The billionaire had been using those vectors for oncology, but the company had also developed vaccine candidates for H1N1, Lassa fever and other viruses. When the outbreak began, he pivoted.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

George Golumbeski (L) and Faheem Hasnain

George Golumbes­ki and Fa­heem Has­nain team up with Ver­tex Ven­tures HC in man­ag­ing $320M of biotech cash

Two longtime biotech veterans are joining a multibillion dollar VC firm in order to help steer its latest fund.

George Golumbeski and Faheem Hasnain have signed on to Vertex Ventures HC as executive advisors, the company announced Thursday, and will assist with their depth of experience in managing $320 million of capital. Both have had previous working relationships with managing partners Carolyn Ng and Lori Hu, which evolved “organically” to get to this point, Ng said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

Noubar Afeyan, Flagship founder and CEO (Victor Boyko/Getty Images)

UP­DAT­ED: Flag­ship launch­es Sen­da Bio­sciences with $88M in back­ing, look­ing to pi­o­neer the field of 'In­ter­sys­tems Bi­ol­o­gy'

Flagship Pioneering has a fresh company out this week, one that aims to lay the groundwork for a whole new discipline.

Senda Biosciences launched Wednesday with $88 million in Flagship cash. The goal? Gain insights into the molecular connections between people and coevolved nonhuman species like plants and bacteria, paving the way for “Intersystems Biology.”

Guillaume Pfefer has been tapped to run the show, a 25-year biotech veteran who comes from GSK after leading the development of the company’s shingles vaccine.

As­traZeneca sells off heart fail­ure and hy­per­ten­sion drugs to Chep­lapharm for $400M

Out with the old and in with the new: AstraZeneca is selling off two heart failure and hypertension drugs to Germany-based Cheplapharm, bagging $400 million and making way for development in other areas.

Cheplapharm paid $200 million for the European rights to Atacand (candesartan cilexetil) and Atacand Plus (candesartan cilexetil and hydrochlorothiazide) back in 2018. They’re now doubling that amount for commercial control in more than 70 countries.

News brief­ing: Ax­o­vant faces months of de­lay on lead Parkin­son's gene ther­a­py; Chi­nese CAR-T biotech nabs $100M

One of Axovant’s top gene therapy prospects for its second act is hitting a roadblock that could push its clinical timelines back by almost a year.

In an update, the biotech said it was informed about delays in CMC data and third-part fill-finish issues around mid-October by its manufacturing partner, Oxford Biomedica. Axovant has been developing a suspension-based process for the Parkinson’s drug; with that taking longer than expected, it now believes “it is unlikely that its planned randomized, sham-controlled trial of AXO-Lenti-PD will enroll patients by the end of calendar year 2021.”

Ugur Sahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

Covid-19 roundup: Flush with $486M con­tract, As­traZeneca signs Lon­za up to man­u­fac­ture an­ti­bod­ies; BioN­Tech's Ugur Sahin ex­pects vac­cine da­ta 'in a fort­night'

Days after scoring a $486 million BARDA contract to develop and manufacture its long-acting antibody combo for Covid-19, AstraZeneca has tapped Lonza to produce the drug substance at its mid-scale facility in Portsmouth, NH.

The drug, dubbed AZD7442, puts together two antibodies, first discovered by scientists at Vanderbilt University Medical Center, derived from convalescent patients who recovered from a SARS-CoV-2 infection. AstraZeneca licensed them in June and has since further engineered them with half-life extension and reduced Fc receptor binding.

CEO Kenji Yasukawa (Astellas)

In ear­ly blow to Ken­ji Ya­sukawa's R&D re­vamp, Astel­las drops out of the TIG­IT race, cit­ing PhI fail­ure

Just after AstraZeneca jumped into the TIGIT race, Astellas quietly disclosed that it was leaving, dropping out of a hunt for an immunotherapy approach that has shown tantalizing promise but remains largely unproven.

Astellas revealed in their second quarter earnings today that they’ve ended development of the anti-TIGIT antibody they acquired in their up to $400 million buyout of Potenza in 2018. The Japanese pharma had been testing it in combination with Keytruda in a 300-person Phase I study on patients with advanced solid tumors. A smaller study testing the antibody alone was completed, 2 years ahead of schedule, in July.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.