Check­point ther­a­pies be­fore surgery? MD An­der­son team re­ports en­cour­ag­ing ef­fi­ca­cy but wor­ries about tox­i­c­i­ty

Days af­ter the No­bel com­mit­tee hon­ored im­munother­a­py in this year’s med­i­cine prize, MD An­der­son, where No­bel win­ner Jim Al­li­son cur­rent­ly works, has some new hu­man da­ta — and lessons — about a nov­el way to use check­point in­hibitors.

Rod­abe Amaria

While check­point drugs like Op­di­vo (nivolum­ab) and Yer­voy (ip­il­i­mum­ab) are of­ten giv­en to melanoma pa­tients af­ter surgery or when their can­cer is un­re­sectable, re­searchers want­ed to know if ad­min­is­ter­ing them be­fore surgery could be an ef­fec­tive ap­proach.

The short an­swer is yes — but with a big as­ter­isk.

In a Phase II study in­volv­ing pa­tients who have reached high-risk stage 3 of the dead­ly skin can­cer, MD An­der­son re­searchers gave 12 pa­tients the PD-1 in­hibitor nivolum­ab and an­oth­er 11 a com­bi­na­tion of nivolum­ab and ip­il­i­mum­ab, which tar­gets CT­LA-4.

Michael Tet­zlaff

In­ves­ti­ga­tors ob­served that com­bined check­point block­ade was “much more ef­fec­tive,” with 8 pa­tients in the arm see­ing their tu­mor shrink and 5 of them show­ing no ev­i­dence of dis­ease at surgery. It’s how­ev­er a re­sult marred by no­table tox­i­c­i­ty — 8 ex­pe­ri­enced grade 3 side ef­fects, caus­ing de­lays in dos­ing and surgery.

The sin­gle-agent an­ti-PD-1 group, mean­while, showed “mod­est re­sponse rates” at 25% tu­mor shrink­age or dis­ap­pear­ance. On­ly 1 pa­tient in the group had grade 3 side ef­fects, but 2 oth­ers pro­gressed to stage 4 metasta­t­ic melanoma be­fore they could get to surgery — a cause for con­cern.

“It is clear from this tri­al that we need to fur­ther op­ti­mize this treat­ment ap­proach,” said Rod­abe Amaria, co-first au­thor and as­sis­tant pro­fes­sor at MD An­der­son’s de­part­ment of melanoma med­ical on­col­o­gy.

Why does it mat­ter whether the check­point drugs are giv­en be­fore or af­ter surgery? Here Michael Tet­zlaff, a pathol­o­gy pro­fes­sor and se­nior au­thor on the study, ex­plains:

The ad­van­tage of a neoad­ju­vant ap­proach in this set­ting is that it en­ables an in­ter­val eval­u­a­tion of the tu­mor cells af­ter ther­a­py to de­ter­mine the ex­tent to which those tu­mor cells re­spond­ed to the ther­a­py in re­al time and pre­dict which pa­tients are like­ly to ex­pe­ri­ence durable re­spons­es go­ing for­ward. It al­so pro­vides us the tis­sue re­sources to de­ter­mine why tu­mors may not re­spond to ther­a­py and thus tai­lor ther­a­pies go­ing for­ward as we learn more about re­sis­tance.

The high oc­cur­rence of side ef­fects forced in­ves­ti­ga­tors to close the tri­al ear­ly, but they note that over­all sur­vival at 24 months was 100% in the com­bo arm and 75% in the nivolum­ab arm. In a re­designed study, they re­placed ip­il­i­mum­ab with re­latlimab (an LAG3 in­hibitor from Bris­tol-My­ers Squibb) an­tic­i­pat­ing a bet­ter safe­ty pro­file.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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J&J ad­comm live blog: J&J is al­so test­ing a two-dose vac­cine. What hap­pens if it's more ef­fec­tive?

J&J has spent the day touting the data behind their Covid-19 vaccine, but one advisor pointed that, in a few months, another batch of data could force them into a curious dilemma.

J&J was the only major vaccine developer to attempt to produce a single-dose vaccine, a huge asset when trying to rapidly inoculate the world against an ongoing public health threat, but they hedged their bets. Alongside their main Phase III trial, they also launched another that would test two doses, each spaced two months apart.

Genen­tech plots $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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