Steven Kelly, Carisma Therapeutics CEO

Con­tin­u­ing push be­yond Covid-19 vac­cines, Mod­er­na part­ners with 'CAR-M' biotech on in vi­vo can­cer cell ther­a­pies

Since com­ing in­to a mas­sive wind­fall with its Covid-19 vac­cines, Mod­er­na has been look­ing for ways to ex­pand its mR­NA tech­nolo­gies in­to oth­er promis­ing ar­eas. On Mon­day, the biotech took its next step to­ward that goal.

Mod­er­na is part­ner­ing with Caris­ma Ther­a­peu­tics on a huge slate of “CAR-M” pro­grams to treat can­cer, the com­pa­nies an­nounced Mon­day morn­ing, promis­ing $45 mil­lion up­front and $35 mil­lion in eq­ui­ty. Though the amount of mile­stones was not spec­i­fied, the biotechs not­ed Mod­er­na has the op­tion to nom­i­nate up to 12 tar­gets for de­vel­op­ment.

Caris­ma will lead pre­clin­i­cal and dis­cov­ery ef­forts while Mod­er­na will take charge for clin­i­cal stud­ies and po­ten­tial com­mer­cial­iza­tion.

“It’s a clear tech­nol­o­gy fit for our mR­NA LNP plat­form,” Rose Lough­lin, Mod­er­na SVP of re­search and ear­ly de­vel­op­ment, told End­points News of the deal. “By part­ner­ship, it re­al­ly lets us quick­ly ex­pand the reach of that plat­form … It’s ide­al for this type of ap­pli­ca­tion, giv­en what they can do. They re­al­ly com­ple­ment our cur­rent on­col­o­gy port­fo­lio.”

Stéphane Ban­cel

The Covid-19 vac­cine has turned Mod­er­na from a biotech with no ap­proved prod­ucts in­to a com­pa­ny worth more than $87 bil­lion as of Mon­day morn­ing — and its CEO, Stéphane Ban­cel, in­to a multi­bil­lion­aire. Pri­or to Mon­day, Mod­er­na al­ready had a few on­col­o­gy pro­grams un­der its belt, in­clud­ing can­cer vac­cines and ex­per­i­men­tal ther­a­peu­tics in­ject­ed di­rect­ly in­to tu­mors.

But Mon­day’s deal marks a new step in that port­fo­lio ex­pan­sion, push­ing Mod­er­na in­to in vi­vo cell ther­a­py tech­nol­o­gy. When the plat­forms are used to­geth­er, Lough­lin said, the mR­NA and LNPs will be used to de­liv­er the CAR-M ther­a­pies, where ‘M’ stands for mono­cytes, a class of in­nate im­mune cells.

“As we think about this ap­pli­ca­tion, in im­muno-on­col­o­gy, it is very much di­rect­ing the im­mune im­pact of these cells to the tu­mor, chang­ing that tu­mor mi­croen­vi­ron­ment and then uti­liz­ing the rest of the im­mune sys­tem, re­al­ly train­ing it to fight the tu­mor,” Lough­lin said. “They’re al­so pre­sent­ing anti­gens from that can­cer cell.”

For Caris­ma, the part­ner­ship marks the next step in the com­pa­ny’s growth, CEO Steve Kel­ly told End­points. The biotech, launched back in 2017 to de­vel­op sol­id tu­mor cell ther­a­pies us­ing CARs and macrophages, put its first pro­gram in­to the clin­ic last year for an au­tol­o­gous CAR-M tar­get­ing HER2-ex­press­ing tu­mors.

Mono­cytes, though, are the pre­cur­sor to macrophages, Kel­ly not­ed, es­sen­tial­ly a pro­drug for the white blood cells. The com­pa­nies will fo­cus on de­liv­er­ing mR­NA ex­pres­sion for CARs to mono­cytes in cir­cu­la­tion, which will then “traf­fic to the tu­mor and dif­fer­en­ti­ate in­to macrophages at that point,” Kel­ly said.

The way the two plat­forms fit to­geth­er “comes down to the speci­fici­ties of the lipid nanopar­ti­cle,” Kel­ly added.

It re­mains to be seen whether Mod­er­na’s suc­cess­es in Covid-19 can be repli­cat­ed in oth­er fields, but ear­ly re­turns have not al­ways im­pressed in­vestors. Last month, Mod­er­na re­leased da­ta for its mR­NA flu shots tout­ing sig­nif­i­cant boost­ing of an­ti­bod­ies, but they didn’t ap­pear to of­fer any clear ad­van­tages over al­ready ap­proved jabs.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Craig Thompson, Cerevance CEO

UP­DAT­ED: Mer­ck makes first big splash for Alzheimer’s drug R&D since 2017 fail, ink­ing re­search pact with Cere­vance

For the first time since discontinuing its late-stage Alzheimer’s program, Merck has found promise on the path forward in the memory-robbing disease.

After a Phase III flop of its drug verubecestat, the New Jersey Big Pharma axed the study in early 2018. More than four years later, the company is ready to sign up for another pact to test the waters of the befuddling disease.

This time, there’s $1.1 billion in biobucks on the line and a target that its partner says no other biopharma is looking at en route to finding the next treatment for Alzheimer’s, a neuroscience field that has hit hurdle after hurdle for decades.

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Joachim Kreuzburg, Sartorious CEO

On an ex­pan­sion spree, Ger­man man­u­fac­tur­er Sar­to­rius makes $500M+ pur­chase of cell cul­ture me­dia play­er

Over the past year, the German-based life science group Sartorius has made several moves to grow the company in the cell and gene therapy space, and its latest move sees the company continuing that track as it is committing to a nine-figure deal to bring UK-based Albumedix under its wing.

The deal will have Sartorius acquiring 100% of the company from private investors for £415 million, or around $502 million. Albumedix, based in the city of Nottingham, UK, is a manufacturer of albumin-based products. Albumin serves as a major ingredient in cell culture media and is used as an animal-free additive in the manufacturing of vaccines, cell therapies and viral therapies. The transaction is expected to close before the end of Q3 of 2022.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Albert Bourla, Pfizer CEO (Laurent Gillieron/Keystone via AP)

Break­ing: Pfiz­er in hot pur­suit of a $5B buy­out of Glob­al Blood Ther­a­peu­tics — re­port

Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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HHS Secretary Xavier Becerra (Patrick Semansky/AP Images)

US weighs new route of ad­min­is­tra­tion for mon­key­pox vac­cine as cas­es climb — re­port

Less than a week after HHS Secretary Xavier Becerra declared monkeypox a national health emergency, reports have emerged that the US plans to extend its vaccine supply by opting for a different route of administration.

Officials are expected to call for intradermal injection of Bavarian Nordic’s Jynneos vaccine — the only shot approved specifically for monkeypox in the US — as opposed to subcutaneous injection, unnamed sources told both the New York Times and Washington Post on Tuesday.