AffyImmune CEO Moonsoo Jin (L) and COO Eric von Hofe

Tiny play­er picks up $30M to go af­ter CAR-T's biggest chal­lenges

Of all the chal­lenges as­so­ci­at­ed with reengi­neer­ing CAR-T ther­a­pies — which have been wild­ly suc­cess­ful in treat­ing cer­tain blood can­cers — to at­tack sol­id tu­mors, tox­i­c­i­ty of­ten ranks near the top.

“If there is no ther­a­peu­tic win­dow, the tri­al will be ter­mi­nat­ed,” Si­mone Song, founder and man­ag­ing part­ner at ORI Cap­i­tal, told End­points News.

Si­mone Song

It was the rea­son why ORI, a Hong Kong-based health­care VC firm fo­cused on can­cer, meta­bol­ic dis­or­ders and neu­rode­gen­er­a­tive dis­eases, de­cid­ed to in­cu­bate a start­up by the name of Affy­Im­mune back in 2017. And it’s why Song’s team is hand­ing over an­oth­er $30 mil­lion to fund a first-in-hu­man tri­al that kicked off late last year and send a sec­ond CAR-T ther­a­py in­to the clin­ic.

The is­sue un­der­ly­ing CAR-T’s tox­i­c­i­ty prob­lem has been well-doc­u­ment­ed. While hema­to­log­i­cal ma­lig­nan­cies can be eas­i­ly hunt­ed down by mark­ers like CD19 and BC­MA (and clin­i­cians can pre­vent side ef­fects sim­ply by wip­ing out B cells, the on­ly oth­er cell type ex­press­ing those anti­gens), it’s much hard­er to dis­tin­guish be­tween sol­id tu­mor cells and or­gans. Pro­gram­ming the CAR-T cells to at­tack any cell bear­ing those tu­mor-as­so­ci­at­ed anti­gens in­evitably hurts nor­mal cells, too. Tu­mor-spe­cif­ic anti­gens have been elu­sive.

Co-found­ed by two sci­en­tists who worked to­geth­er as post­docs at Tim Springer’s Har­vard lab, Affy­Im­mune’s pro­posed so­lu­tion ze­roes in on the binders on CAR-T.

Gang Song

When study­ing the in­ter­ac­tion be­tween an anti­gen called ICAM1 and its nat­ur­al lig­and, Moon­soo Jin and Gang Song test­ed mul­ti­ple “affin­i­ty vari­ants” — sin­gle chain mon­o­clon­al an­ti­bod­ies sport­ing dif­fer­ent struc­tures — against ICAM1. What they found was that the tight­est binders, which have tra­di­tion­al­ly been fa­vored, are not nec­es­sar­i­ly the best. Rather, some of the weak­er binders (which they de­scribe as be­ing in the nanomo­lar range) ap­peared to be bet­ter at elim­i­nat­ing tu­mors.

Be­sides, these weak­er binders would spare healthy cells with low ex­pres­sion of the tar­get in fa­vor of tu­mor cells, which tend to have much high­er ex­pres­sion, said Er­ic von Hofe, pres­i­dent and COO. By tai­lor­ing an affin­i­ty lev­el to each tar­get based on its ex­pres­sion on nor­mal cells, Affy­Im­mune be­lieves its tun­ing method draws that thin line for CAR-T cells to sep­a­rate friend from foe.

“For each tar­get we look at, es­sen­tial­ly we’re clean­ing them up,” he said.

They al­so just look more like the nat­ur­al re­cep­tors im­mune cells use to bind to tu­mors, said von Hofe, mim­ic­k­ing the phys­i­o­log­i­cal in­ter­ac­tion. That comes with oth­er in­di­rect ben­e­fits: The T cells don’t get over­stim­u­lat­ed or ex­haust­ed too quick­ly, and the­o­ret­i­cal­ly can func­tion for longer, killing more can­cer cells.

“It’s an easy con­cept, but to [get to] the ex­act lev­el it takes a lot of work,” Song said. “It has tak­en them a lot of work to find the ex­act right lev­el.”

The Se­ries A+ is ad­mit­ted­ly mod­est by CAR-T stan­dards these days, es­pe­cial­ly for a clin­i­cal-stage out­fit. Over the last four and a half years, von Hofe — the first em­ploy­ee to join Jin, now the CEO — has grown the crew to nine, main­tain­ing a lean op­er­a­tion fo­cused on se­cur­ing the first clin­i­cal proof-of-con­cept.

Affy­Im­mune is first test­ing its lead drug in thy­roid can­cer, but said ICAM1 is found in a range of oth­er can­cer types rang­ing from gas­tric can­cer to triple neg­a­tive breast can­cer. At the same time, there’s a sec­ond part to its “tune and track” plat­form — a so­mato­statin re­cep­tor that al­lows in­fused CAR-T cells to be “seen” in re­al time through an FDA-sanc­tioned ra­dio la­bel trac­er and PCP or CT scans.

“Down the road, I mean pos­si­bly we could see about com­bin­ing with oth­er tech­nolo­gies if there’s a true en­hance­ment, but we’ve been pret­ty — I wouldn’t say con­ser­v­a­tive, but we’ve just stuck with things that are known to work,” von Hofe said. “Some oth­er com­pa­nies are try­ing to do all kinds of very high tech things, and it’s very ex­cit­ing, and they bring in a lot of mon­ey do­ing it. As I men­tioned, Affy­Im­mune’s fo­cus has been get­ting func­tion­al CAR-T cells that are more func­tion­al than oth­er CAR-T cells out there, with this affin­i­ty tune, tracked, get those in­to the clin­ic, show there’s a ben­e­fit to the pa­tient, and then ex­pand on that.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Luc Boblet, Egle Therapeutics CEO

A new Treg play­er emerges with $46M and back­ing from Take­da

In recent years, the chorus of biotechs and Big Pharma backers targeting regulatory T cells — also known as “Tregs” — for cancer and autoimmune diseases has only grown louder.

The newest voice is from Egle Therapeutics, which sang out a $46.4 million Series A round on Friday led by LSP and Bpifrance through their InnoBio 2 fund. Takeda’s venture arm also chipped in, about a year after the pharma struck a research pact with the Paris-based upstart.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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