Piv­otal fail­ure trig­gers job cuts at San Diego-based Toca­gen

Toca­gen is cir­cling the drain, fol­low­ing the crush­ing late-stage fail­ure of its ex­per­i­men­tal brain can­cer ther­a­py last month. On Thurs­day, the San Diego-based com­pa­ny slashed its work­force by 65%.

Its two-part ther­a­py was be­ing test­ed in pa­tients with re­cur­rent high-grade glioma un­der­go­ing re­sec­tion in the To­ca 5 study. On av­er­age, pa­tients on the Toca­gen reg­i­men ac­tu­al­ly did not live as long as those giv­en stan­dard treat­ment (11.1 months me­di­an com­pared to 12.2 months). In ad­di­tion, the com­pa­ny’s ther­a­py hit a haz­ard ra­tio of 1.06, re­flect­ing an in­creased risk to pa­tients, along with an un­sa­vory p-val­ue of 0.6154.

Toca­gen’s tech­nol­o­gy em­ploys retro­vi­ral repli­cat­ing vec­tors, or RRVs, which are en­gi­neered to se­lec­tive­ly de­liv­er ther­a­peu­tic genes in­to can­cer cells. The ex­per­i­men­tal brain can­cer ther­a­py in ques­tion com­bines an RRV, called To­ca 511, with an in­ves­ti­ga­tion­al small mol­e­cule, To­ca FC.

To­ca 511 is de­signed to iso­late can­cer cells and de­liv­er a gene for the en­zyme, cy­to­sine deam­i­nase (CD). On­ly in­fect­ed can­cer cells are meant to car­ry and spawn CD. When To­ca FC en­coun­ters CD, it is tai­lored to trans­form in­to the an­ti-can­cer drug 5-FU, and in turn to an­nex the tu­mor.

Fol­low­ing the lay­offs, Toca­gen — which made its pub­lic de­but in 2017 — is left with 30 em­ploy­ees. They will fo­cus on the Phase II/III tri­al of To­ca 511-To­ca FC in new­ly-di­ag­nosed glioblas­toma (HGG) pa­tients — as well as an ear­ly-stage study in blad­der can­cer.

“Giv­en the To­ca 5 miss on both pri­ma­ry and sec­ondary end­points (re­lat­ing to over­all sur­vival and dura­bil­i­ty of re­sponse, re­spec­tive­ly), we main­tain low ex­pec­ta­tions (0% POS) for the To­ca 511 & To­ca FC reg­i­men in HGG in the ab­sence of new in­for­ma­tion,” Chardan an­a­lysts wrote in a note on Thurs­day.

The com­pa­ny plans to present the com­plet­ed analy­sis of the To­ca 5 tri­al at the 2019 So­ci­ety for Neu­ro-On­col­o­gy an­nu­al meet­ing in No­vem­ber, it said.

Brain can­cer is no­to­ri­ous­ly hard to treat and re­mains the dead­liest of can­cers, de­spite decades of re­search. Tu­mors are of­ten lo­cat­ed be­yond the reach of even the most con­sum­mate neu­ro­sur­geon, and pro­tect­ed by the blood-brain bar­ri­er, there­by thwart­ing ex­po­sure to sys­temic chemother­a­py. In ad­di­tion, the par­tic­u­lar de­vel­op­men­tal, ge­net­ic, and mi­cro-en­vi­ron­men­tal ecosys­tem in the brain ren­ders tu­mors re­sis­tant to tra­di­tion­al weapons in the on­col­o­gist’s ar­ma­men­tar­i­um.

In its sec­ond quar­ter re­port — pub­lished in Au­gust — Toca­gen in­di­cat­ed it had cash, cash equiv­a­lents and mar­ketable se­cu­ri­ties of $68.3 mil­lion, as of June 30. Shares of the drug de­vel­op­er $TO­CA have been lan­guish­ing in pen­ny stock ter­ri­to­ry since its piv­otal fail­ure dis­clo­sure in Sep­tem­ber.

So­cial im­age: Shut­ter­stock

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

Credit: Shutterstock

How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

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An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

(Photo courtesy Pfizer)

FDA's vac­cine ad­comm votes al­most unan­i­mous­ly in fa­vor of Pfiz­er's Covid-19 vac­cine for younger chil­dren

The FDA’s Vaccines and Related Biological Products Advisory Committee on Tuesday voted 17-0, with one panelist abstaining, that the benefits of the Pfizer-BioNTech Covid-19 vaccine outweigh the risks for children between the ages of five and 12.

The vote will likely trigger a process that could allow the shots to begin rolling out as early as next week.

The vaccine, which is one-third of the adult Pfizer dose, proved to be about 90% effective in a placebo-controlled trial in which about 1,500 kids in this age range received the vaccine, and only about 12% of those receiving the vaccine had any adverse event. All serious adverse events in the trial were unrelated to the vaccine.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Mod­er­na chips in fur­ther on African vac­cine sup­ply — but ad­vo­cates are call­ing for even more

In a sign of its growing commitment to the continent, Moderna will supply up to 110 million doses of its Covid-19 vaccine to the African Union, the company announced Tuesday. And CEO Stéphane Bancel said it’s just the first step.

“We believe our vaccine can play an important role in addressing the needs of low-income countries given its combination of high Phase 3 efficacy against COVID-19, strong durability in the real-world evidence, and superior storage and handling conditions. We recognize that access to COVID-19 vaccines continues to be a challenge in many parts of the world and we remain committed to helping to protect as many people as possible around the globe,” Bancel said in a statement.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

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Ugur Sahin, AP Images

As pres­sure to share tech­nol­o­gy mounts, BioN­Tech se­lects Rwan­da for lat­est vac­cine site

BioNTech’s first mRNA-based vaccine site in Africa will call Rwanda home, and construction is set to start in mid-2022, the company announced Tuesday at a public health forum.

The German company signed a memorandum of understanding, after a meeting between Rwanda’s Minister of Health, Daniel Ngamije, Senegal’s Minister of Foreign Affairs Aïssata Tall Sall, and senior BioNTech officials. Construction plans have been finalized, and assets have been ordered. The agreement will help bring end-to-end manufacturing to Africa, and as many as several hundred million doses of vaccines per year, though initial production will be more modest.

No­var­tis dumps AveX­is pro­gram for Rett syn­drome af­ter fail­ing re­peat round of pre­clin­i­cal test­ing

Say goodbye to AVXS-201.

The Rett syndrome gene therapy drug made by AveXis — the biotech that was bought, kept separate, then renamed and finally absorbed by Novartis into its R&D division — has been dropped by the biopharma.

In Novartis’ third quarter financial report, the pharma had found that preclinical data did not support development of the gene therapy into IND-enabling trials and beyond. The announcement comes a year after Novartis told the Rett Society how excited it was by the drug — and its potential benefits and uses.

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