Ver­sant de­buts Ridge­line's start­up #4, armed with $30M and al­ter­na­tive TCR cell ther­a­pies for sol­id tu­mors

For all the it­er­a­tions and ad­vances in TCR ther­a­pies for can­cer, any ex­per­i­men­tal treat­ments in­volv­ing T cell re­cep­tors share one trait: By de­f­i­n­i­tion, they on­ly rec­og­nize anti­gens pre­sent­ed as pep­tides on the ma­jor his­to­com­pat­i­bil­i­ty com­plex (MHC) on cells.

Gen­naro De Libero

Ver­sant reck­ons it’s time to ex­pand the ar­se­nal. With $30 mil­lion in ini­tial fund­ing, its Ridge­line Dis­cov­ery En­gine in Switzer­land has been work­ing on a non-pep­tidic ap­proach that it says has tu­mor-ag­nos­tic po­ten­tial, es­pe­cial­ly in sol­id tu­mors. They’ve named it Mat­ter­horn, af­ter a Swiss moun­tain as they did with the three oth­er com­pa­nies that have emerged from the Basel-based in­cu­ba­tor.

The key dis­cov­er­ies by found­ing sci­en­tists Gen­naro De Libero and Lu­cia Mori at the Uni­ver­si­ty of Basel have to do with MR1, or MHC class I-re­lat­ed mol­e­cule 1.

When they be­gan prob­ing the pro­tein more than 10 years ago, MR1 was most­ly known for bind­ing to mol­e­cules of bac­te­r­i­al ori­gin — and thus its role in in­fec­tions. But De Libero and Mori pre­dict­ed that en­doge­nous mol­e­cules could be pre­sent­ed as well. And they were right. Not on­ly did they find metabo­lites tied to tu­mor cell pro­lif­er­a­tion that are not found on healthy cells, they al­so stum­bled up­on a class of T cells that could specif­i­cal­ly tar­get MR1.

“We pub­lished that the fre­quen­cy of these cells in the blood is sim­i­lar to the fre­quen­cy of pep­tide-spe­cif­ic T cells,” De Libero told End­points News. “And they were over­looked.”

Be­cause MR1 is iden­ti­cal across hu­mans act­ing as a sur­veil­lance sys­tem for aber­rant me­tab­o­lism, it lends it­self to an off-the-shelf ther­a­py, with no HLA match­ing nec­es­sary.

“The idea then is to gen­er­ate a li­brary of com­pounds that are metabo­lites, that ac­cu­mu­late in the tu­mor, to­geth­er with a li­brary of pre­de­fined T cell re­cep­tors,” he said. “So that if your tu­mor ex­press­es a com­pound A, you will uti­lize re­cep­tor A that you know is spe­cif­ic to that com­bi­na­tion.”

Lu­cia Mori

Al­though Mat­ter­horn’s tar­gets and re­cep­tors are new, the method of get­ting them in­to T cells isn’t. Much like CAR-T and oth­er TCR ther­a­pies, sci­en­tists will knock out en­doge­nous TCR genes and trans­duce T cells with their own re­cep­tors.

Based on the pre­clin­i­cal da­ta he and Mori, the CSO of Mat­ter­horn, along­side 10 staffers have gen­er­at­ed to date, De Libero be­lieves that their li­brary would ul­ti­mate­ly con­sist of a rel­a­tive­ly small num­ber of metabo­lites and cor­re­spond­ing T cell re­cep­tors — “much less than 100” in to­tal.

Alex May­weg

The re­search so far al­so in­di­cates that while cer­tain tu­mors car­ry rare metabo­lites, there are oth­er metabo­lites that are present in a whole bas­ket of dif­fer­ent tu­mors and tis­sues. ‘We don’t want to say that we have the sil­ver bul­let against every­thing here, but it has a breadth that no oth­er T cell ther­a­py right now re­al­ly has,” Alex May­weg, man­ag­ing di­rec­tor at Ver­sant and a board mem­ber at Mat­ter­horn, said.

The plan now is to go through the col­lec­tion of MR1 T cells and re­cep­tors they’ve as­sem­bled and nom­i­nate a lead clin­i­cal can­di­date lat­er this year, aim­ing to be ready for the clin­ic in ear­ly 2022. Mean­while, the Ridge­line team will fade out as Mat­ter­horn grows its in­ter­nal pay­roll to 15 to 20 by the end of this year.

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 have vowed not to let politics get in the way of 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 health agencies under his purview — including the FDA — of their rulemaking 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.

Eli Lilly CSO Dan Skovronsky (file photo)

#ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.

#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.

But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.

The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).

Exelixis CEO Michael Morrissey (file photo)

#ES­MO20: Look out Mer­ck. Bris­tol My­ers and Ex­elix­is stake out their com­bo’s claim to best-in-class sta­tus for front­line kid­ney can­cer

Now that the PD-(L)1 checkpoints are deeply entrenched in the oncology market, it’s time to welcome a wave of combination therapies — beyond chemo — looking to extend their benefit to larger numbers of patients. Bristol Myers Squibb ($BMY} and Exelixis {EXEL} are close to the front of that line.

Today at ESMO the collaborators pulled the curtain back on some stellar data for their combination of Opdivo (the PD-1) and Cabometyx (the TKI), marking a significant advance for the blockbuster Bristol Myers franchise while offering a big leg up for the team at Exelixis.

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Donald Trump and White House chief of staff Mark Meadows, before boarding Marine One (Getty Images)

Pric­ing deal col­laps­es over Big Phar­ma's re­fusal to is­sue $100 'cash card­s' be­fore the elec­tion — re­port

Late in August, as negotiations on a pricing deal with President Trump reached a boiling point, PhRMA president Stephen Ubl sent an email update to the 34 biopharma chiefs that sit on his board. He wrote that if the industry did not agree to pay for a $100 “cash card” sent to seniors before November, White House chief of staff Mark Meadows was going to tell the news media Big Pharma was refusing to “share the savings” with the elderly — and that all of the blame for failed drug pricing negotiations would lie squarely on the industry.

Dan Skovronsky, Eli Lilly CSO

An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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#ES­MO20: It’s not just Keytru­da any­more — Mer­ck spot­lights 3 top ear­ly-stage can­cer drugs

Any $12 billion megablockbuster in the portfolio tends to overshadow everything else in the pipeline. Which is something Merck can tell you a little bit about.

Keytruda not only dominates the PD-(L)1 field, it looms over everything Merck does, to the point some analysts wonder if Merck is a one-trick pony.

There’s no shortage of Keytruda data on display at ESMO this weekend, but now the focus is shifting to the future role of new drugs and combos in maintaining that lead position for years to come. And the pharma giant has a special focus for 3 early-stage efforts where Roger Perlmutter’s oncology team is placing some big bets.

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