Re­searchers de­vel­op a small-mol­e­cule 'sun­less tan' to guard against skin can­cer

Re­searchers have de­signed a small-mol­e­cule SIK in­hibitor ca­pa­ble of pen­e­trat­ing hu­man skin, which could lead the way to a ‘sun­less tan’ that has the po­ten­tial to re­duce the risk of skin can­cer. The mol­e­cule, de­vel­oped at Mass­a­chu­setts Gen­er­al Hos­pi­tal and the Dana-Far­ber Can­cer In­sti­tute, by­pass­es the de­fec­tive re­cep­tor that pre­vents many fair-skinned peo­ple from tan­ning and stim­u­lates melanin pro­duc­tion fur­ther down the line.

Ex­po­sure to ul­tra­vi­o­let light doesn’t al­ways lead to tan­ning in fair-skinned in­di­vid­u­als be­cause many of them lack a func­tion­al melanocortin 1 re­cep­tor (MC1R). Re­searchers orig­i­nal­ly be­lieved this re­cep­tor and the hor­mone that stim­u­lates it—MC1R lig­and melanocyte stim­u­lat­ing hor­mone (MSH)—were nec­es­sary to pro­duce melanin in re­sponse to UV light ex­po­sure.

Pre­vi­ous re­search showed they could stim­u­late the pig­men­ta­tion in mice that didn’t have a func­tion­al re­cep­tor by ap­ply­ing forskolin, a cyclic AMP ag­o­nist. The mice pro­duced pig­ment with­out the func­tion­ing re­cep­tor, but this ear­li­er mol­e­cule wouldn’t pen­e­trate thick­er hu­man skin to have the same ef­fect.

The team turned to SIK in­hibitors which, like forskolin, work on the same path­way fur­ther down the line than the Mc1R re­cep­tors. SIK in­hibitors were known to pro­duce the same out­come by en­hanc­ing ex­pres­sion of the MITF tran­scrip­tion fac­tor, which reg­u­lates ex­pres­sion of en­zymes that pro­mote biosyn­the­sis of melanin.

David Fish­er, MGH Can­cer Cen­ter

Once the team showed that the SIK in­hibitor had stim­u­lat­ed the path­way to pro­duce melanin in red-haired mice — who, like red-haired hu­mans, gen­er­al­ly don’t tan — they worked with Nathaneal Gray, vice chair of re­search in pe­di­atric on­col­o­gy at Dana Far­ber, to find a small mol­e­cule SIK in­hibitor that was able to pen­e­trate hu­man skin. They rubbed the drug on­to skin sam­ples for eight days, and showed a grad­ual dark­en­ing of the skin. Af­ter they stopped, there was a grad­ual light­en­ing — just like a re­al tan. 

If the mol­e­cule grad­u­ates in­to the clin­ic, it’ll face long odds against an un­yield­ing late-stage fail­ure rate. Should it be­come a prod­uct, some con­sumers might find this mol­e­cule ap­peal­ing for cos­met­ic rea­sons, as it cre­ates a tan us­ing the body’s nat­ur­al mech­a­nism for col­or­ing skin.

Ex­cept MGH re­searcher David Fish­er tells BBC News: “[Our] re­al goal is a nov­el strat­e­gy for pro­tect­ing skin from UV ra­di­a­tion and can­cer … dark pig­ment is as­so­ci­at­ed with a low­er risk of all forms of skin can­cer — that would be re­al­ly huge.”

George Scangos (L) and Marianne De Backer

Pi­o­neer­ing biotech icon George Scan­gos hands in his re­tire­ment pa­pers — and this time it’s for re­al

George Scangos, one of the all-time great biotech CEOs, says the time has come to turn over the reins one last time.

The 74-year-old biotech legend spent close to three decades in a CEO post. The first was at Exelixis — which is still heavily focused on a drug Scangos advanced in the clinic. The second “retirement” was at Biogen, where he and his team were credited with a big turnaround with the now fading MS blockbuster Tecfidera. And the third comes at Vir, where he traded in his Big Biotech credentials for a marquee founder’s role back on the West Coast, hammering out a Covid-19 alliance with Hal Barron — then R&D chief at GSK — and breaking new ground on infectious diseases with some high-powered venture players.

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Jeanne Loring, director of the Center for Regenerative Medicine (Credit: Jamie Scott Lytle)

A stem cell pi­o­neer sent an ex­per­i­ment in­to space. Pa­tients are the next fron­tier

Last July, Jeanne Loring stood on a dirt road surrounded by Florida swampland and watched as a nearby SpaceX rocket blasted into the sky. The payload included a very personal belonging: cell clusters mimicking parts of her brain.

For more than two decades, Loring has been at the forefront of a stem cell field that always seems on the brink of becoming the next thing in medicine, but has been slow to lift off.

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FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

In­vestor 'misalign­men­t' leads to tR­NA biotech's shut­ter­ing

A small biotech looking to carve a lane in the tRNA field has folded, an investor and a co-founder confirmed to Endpoints News.

Similar to Flagship’s Alltrna and other upstarts like Takeda-backed hC Bioscience, the now-shuttered Theonys was attempting to go after transfer RNA, seen as a potential Swiss Army knife in the broader RNA therapeutics space. The idea is that one tRNA drug could be used across a galaxy of disorders and diseases.

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#JPM23: What's re­al­ly dri­ving the cost of health­care and drugs in 2023?

Executive Editor Drew Armstrong spoke with PhRMA CEO Steve Ubl, EmsanaRx CEO Greg Baker and ICER President Steve Pearson about how the debate over drug costs has changed (or not) in the last decade, the shifting payer landscape and why there seems to be so little movement on drug rebates. This transcript has been edited for brevity and clarity.

Drew Armstrong:

So first of all, thank you to everybody for being here and for our panel for being here. Incredibly excited to have this discussion on the cost of healthcare and drugs and what’s driving that. We’re here with Steve Ubl, the head of PhRMA. Thank you so much. Steve Pearson from ICER, and Greg Baker from EmsanaRx. I want to start this conversation with a little bit of a personal reminiscence. So about almost 10 years exactly. I was a reporter back in my previous job and I was covering drug pricing and Gilead had just launched their hepatitis C drug and I was having a conversation with another Steve over at Express Scripts and he made some comments essentially about how they intended to launch a price war over hepatitis C therapies.

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Pa­tient death spurs tri­al halt for Ma­gen­ta Ther­a­peu­tics

Magenta Therapeutics is pausing an early-stage clinical trial after a patient died. The death was deemed to be possibly related to its drug, MGTA-117.

The biotech said the pause of the Phase I/II trial is voluntary and gives it time to review all available data before deciding what to do next. It’s also reported the known information to the FDA.

The dose-escalation trial was designed to test whether MGTA-117, an antibody-drug conjugate, could serve as a more targeted alternative to high-intensity chemotherapy as a conditioning agent for cancer patients who are set to receive a stem cell transplant. It recruited patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.

In a win for Re­gen­eron, No­var­tis' sy­ringe for AMD drug de­clared 'un­patentable'

Regeneron has won a patent case against Swiss pharma giant Novartis over the delivery system for its eye drug Eylea.

The US Patent Trial and Appeal Board ruled that Novartis’ pre-filled syringe for injecting its eye medication Lucentis was “unpatentable” and handed the victory to Regeneron and its AMD drug Eylea.

In the initial complaint in 2020, Novartis alleged to the US International Trade Commission that certain pre-filled syringes for the intravitreal injection, and ultimately Regeneron’s delivery system for Eylea, were infringing on Novartis’ patent. Regeneron filed a petition to review Novartis’ claims in 2021.

'Tis the sea­son: GSK ad­dress­es win­ter virus surges with celebri­ty and in­flu­encer vac­cine aware­ness cam­paigns

GSK is rounding up the usual suspects this winter — flu, respiratory syncytial and even shingles viruses — for multiple marketing efforts all aimed at encouraging vaccinations.

Mom influencers take center stage in its “Flu is a Family Affair” campaign to reach family decision-makers or “chief health officers.” GSK is asking them in the digital campaign to take care of themselves, and take the family along, when they go to the pharmacy or doctor’s office for a flu vaccine.

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