Al­lied with Genen­tech and Pfiz­er on dis­cov­ery deals, pro­tein degra­da­tion crew at Arv­inas looks for $100M IPO ahead of PhI start

The next wave of biotech IPOs is start­ing to swell to­day as the pro­tein degra­da­tion crew at Arv­inas jumps in with a $100 mil­lion of­fer­ing. And once again we’re see­ing a dis­cov­ery com­pa­ny go­ing ear­ly — with their first Phase I pro­gram still out ahead.

Arv­inas gained a con­sid­er­able amount of at­ten­tion for two deals with Genen­tech and Pfiz­er, which we now know came with a rel­a­tive­ly small up­front and big back end num­bers.

John Hous­ton

The big Roche sub­sidiary stepped up first in 2015, then re­jigged their deal in 2017. Genen­tech can tap up to 10 tar­gets in the dis­cov­ery al­liance, which was worth $11 mil­lion to get start­ed and an­oth­er $34.5 mil­lion pay­day to ex­tend last year. And there’s $156 mil­lion in col­lec­tive mile­stones for each tar­get — should it go all the way in­to the mar­ket.

Pfiz­er is in for less. The phar­ma gi­ant hand­ed over $28 mil­lion to get start­ed and com­mit­ted up to $775 mil­lion in de­vel­op­ment and com­mer­cial mile­stones for the pack­age. That an­swers one of the unan­swered ques­tions from Arv­inas’ days as a pri­vate start­up.

Pro­tein degra­da­tion has be­come a hot field in on­col­o­gy, as new com­pa­nies look to do bet­ter than the orig­i­nal set of ther­a­pies that have hit the mar­ket. In Arv­inas’ case, CEO John Hous­ton has been go­ing af­ter prostate can­cer and breast can­cer, with their first Phase I for the lead prostate can­cer ther­a­py lin­ing up for a start in ear­ly 2019.

Craig Crews

Arv­inas is by no means play­ing so­lo in the sec­ond-gen pro­tein degra­da­tion field. Ri­vals to the pro­tein degra­da­tion ti­tle in­clude C4 Ther­a­peu­tics — out of Jay Brad­ner’s lab at Dana Far­ber be­fore he took the helm at NI­BR — and the start­up Kymera. And not sur­pris­ing­ly, Brad­ner — who now runs NI­BR — re­cent­ly forged a close re­la­tion­ship with UC San Fran­cis­co on pro­tein degra­da­tion as well.

They’re look­ing to use an E3 lig­ase to dis­patch tar­get pro­teins through the cell’s nat­ur­al “garbage dis­pos­al” called the ubiq­ui­tin-pro­tea­some sys­tem, knock­ing them en­tire­ly out of the pic­ture and do­ing a much bet­ter job than what you get from mere pro­tein in­hi­bi­tion.

5AM and Canaan have the biggest stakes in the com­pa­ny, at 18.5% each. Craig Crews, who pro­vid­ed the sci­en­tif­ic in­sights from his Yale lab, has 8.9% while RA Cap­i­tal is in for 8%, Or­biMed has 6% and Nex­tech V On­col­o­gy is down for 5%. CEO Hous­ton has a 4.5% batch of stock.

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.

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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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James Peyer, Cambrian CEO

Brent Saun­ders joins $100M Se­ries C for a com­pa­ny out to be the Bridge­Bio of ag­ing

About a year ago, James Peyer, a CEO and co-founder of the little known longevity biotech Cambrian Biopharma, was trying to find some R&D talent last year when he met with more than a bit of experience in that department: David Nicholson, the former R&D chief of the erstwhile pharma giant Allergan.

It turned out Nicholson already had an interest in Peyer’s field. In their Allergan days, he and COO Brent Saunders held weekly meetups where they tried to figure out how to take the company’s dominance in aesthetics — which, until recently, was often what people meant by anti-aging science — and expertise with more traditional drug development, and use it to make drugs that extend people’s lifespan.

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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.