A quiver of ar­rows for im­mune dis­or­ders: Pan­dion scores $80M in fresh fund­ing

Sci­en­tists be­gan with mak­ing re­com­bi­nant ver­sions of nat­u­ral­ly-oc­cur­ring hu­man pro­teins, then grad­u­at­ed to mon­o­clon­al an­ti­bod­ies. Now, rather than repli­cat­ing moi­eties with­in the body, re­searchers are mod­i­fy­ing these mol­e­cules to have pre­cise bi­ol­o­gy in a func­tion­al man­ner.

This tech­nol­o­gy, re­ferred to as bis­pe­cif­ic an­ti­bod­ies, is al­ready be­ing em­ployed to fight can­cer. In ear­ly 2018, Pan­dion Ther­a­peu­tics was born to re­verse-en­gi­neer the sci­ence in­to the realm of au­toim­mune and in­flam­ma­to­ry dis­or­ders.

Rahul Kakkar

Mon­o­clon­al an­ti­bod­ies are de­signed to in­hib­it a path­way, but Pan­dion is tak­ing a mol­e­cule that the body cre­ates, and en­gi­neer­ing it for the bi­ol­o­gy that we want, said com­pa­ny chief Rahul Kakkar in an in­ter­view.

As the com­pa­ny shep­herds its lead ther­a­py in­to pa­tients, on Wednes­day it raised a meaty $80 mil­lion in a fresh round of fi­nanc­ing.

Pan­dion, which counts Astel­las as a part­ner, has cre­at­ed com­po­nents that can be mixed and matched to cre­ate mol­e­cules that have both the bi­o­log­ic and the chem­i­cal ther­a­peu­tic prop­er­ties that we want, Kakkar ex­plained.

“The way I like to think about it is our mol­e­cules rep­re­sent ar­rows, with­in a quiver of ar­rows that rep­re­sents our pipeline,” he said. “So each of these ar­rows has an ar­row­head. The ar­row­head is an en­gi­neered vari­ant of some­thing our bod­ies nat­u­ral­ly use to con­trol the im­mune sys­tem.”

The ar­row­head in the com­pa­ny’s lead pro­gram — PT101 — is a mu­tat­ed vari­ant of in­ter­leukin two. Nat­u­ral­ly, the body us­es IL-2 to ex­pand reg­u­la­to­ry T cells and to en­hance con­ven­tion­al pro-in­flam­ma­to­ry T cells. Pan­dion’s IL-2 two has been en­gi­neered to be high­ly spe­cif­ic for reg­u­la­to­ry T cells, but to have no ef­fect on the oth­er cells. The ther­a­py is cur­rent­ly be­ing eval­u­at­ed in healthy vol­un­teers — and if all goes well, come 2021, the com­pound will be test­ed in ul­cer­a­tive col­i­tis pa­tients.

The ar­row­head is in charge of the bi­ol­o­gy, but the tail gives the ar­row­head phar­ma­cother­a­peu­tic prop­er­ties that we want. “So we can mar­ry an FC fu­sion, for in­stance, which gives half-life ex­ten­sion, so then that ar­row­head re­sides with­in the sys­temic cir­cu­la­tion, has sys­temic im­mune-mod­u­la­to­ry prop­er­ties and be­haves like an in­jectable bi­o­log­ic,” Kakkar said.

The next junc­ture, which Pan­dion has un­der de­vel­op­ment, is cre­at­ing a bi­func­tion­al or bis­pe­cif­ic, so the tail end ac­tu­al­ly has a func­tion, rather than just half-life ex­ten­sion.

“That tail…is de­signed as a teth­er or a dock, where it binds the ar­row­head with­in an or­gan of in­ter­est so we can, there­fore, guide the ar­row­head in­to spe­cif­ic or­gan sys­tems,” Kakkar said. “So, for in­stance, we can guide it in­to the be­ta cells of the pan­creas, which is where our col­lab­o­ra­tion with Astel­las fo­cus­es.”

The word Pan­dion is the genus name for the os­prey (or a sea hawk), a brown-and-white bird of prey. Spread­ing its wings, it swoops down to wa­ter sur­faces to seize un­sus­pect­ing fish us­ing its talons. “The im­age of a very pre­cise hit with wing­spread ba­si­cal­ly looks like an an­ti­body bind­ing to a very spe­cif­ic lo­cal­iza­tion in ge­og­ra­phy and so that’s ex­act­ly what our mol­e­cules do par­tic­u­lar­ly in the bis­pe­cif­ic for­mat,” said Kakkar.

The Se­ries B was led by Ac­cess Biotech­nol­o­gy, Box­er Cap­i­tal, RA Cap­i­tal and Or­biMed and in­clud­ed the par­tic­i­pa­tion of Po­laris Part­ners, Ver­sant Ven­tures, Roche Ven­ture Fund, SR One, JDRF T1D Fund and BioIn­no­va­tion Cap­i­tal. The Boston-based start­up raised $58 mil­lion in Jan­u­ary 2018.

De­spite the dis­rup­tions faced by the on­go­ing coro­n­avirus pan­dem­ic, since the biotech in­dus­try is con­sid­ered es­sen­tial in Boston, the com­pa­ny con­tin­ues to work on its com­pounds, al­though all non-lab per­son­nel are work­ing re­mote­ly.

“Frankly speak­ing, the need of pa­tients suf­fer­ing from au­toim­mune dis­ease con­tin­ues and so as long as that need is there, we con­tin­ue to be fo­cused on ex­e­cut­ing on our goals,” Kakkar said.

That be­ing said, work­ing from home is hard­ly a walk in the park. ” I think we’re all sup­port­ing each oth­er as best we can, but I think it’s a chal­lenge for every­one.”

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Francesco De Rubertis

Medicx­i's David Grainger and Francesco De Ru­ber­tis pump €200M in­to six com­pa­nies and what they say is a first-of-its kind fund

In what they’re billing as a first for biotech, David Grainger, Francesco De Rubertis and their team at Medicxi have put down €200 million to sweep up stakes in six companies from their predecessor VC and pump new money into them.

Medicxi didn’t disclose which companies it was investing in but the portfolio draws from Index Ventures Life VI, one of the last funds the Medicxi team launched while they were still part of the multinational, tech-focused VC firm Index Ventures. That team kept advising Index on their life sciences portfolio even after they spun out to form their own firm in the middle of 2016.

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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.