Backed by a biotech leg­end, two young en­tre­pre­neurs tack­le one of the Holy Grails of R&D

Joshua Co­hen

It’s not of­ten that two re­cent col­lege grads can come up with enough cash and con­nec­tions to run a Phase II study of a new com­bi­na­tion drug for a tough and dead­ly dis­ease like ALS. But with some back­ing by biotech leg­end Hen­ri Ter­meer and $8 mil­lion in ven­ture cash and grant mon­ey, Justin Klee and Josh Co­hen say they’re ready to turn what start­ed out as an un­der­grad­u­ate sci­ence project at Brown in­to a clin­i­cal re­al­i­ty in a mat­ter of months at a start­up dubbed Amy­lyx.

The key com­po­nent in all this, the mon­ey to start dos­ing pa­tients, comes from a $5 mil­lion Se­ries A led by Morn­ing­side Ven­ture with con­tri­bu­tions from the ALS In­vest­ment Fund and for­mer Gen­zyme CEO Ter­meer. Com­bined with a $3 mil­lion grant from the ALS Ac­cel­er­at­ed Ther­a­peu­tics Ini­tia­tive and some dis­count pric­ing from a net­work of hos­pi­tals en­gaged in ALS work, and Klee and Co­hen say they’ve reached the thresh­old of a mid-stage tri­al that will look for both ef­fi­ca­cy and safe­ty da­ta.

Justin Klee

“It is atyp­i­cal,” Klee al­lows in our tele­phone in­ter­view this morn­ing. But the two young en­tre­pre­neurs are prepar­ing to take a shot at ALS on a bud­get that most Big Phar­mas would spend on pre­clin­i­cal work. And they say their work could have ap­pli­ca­tions for Alzheimer’s, an­oth­er dev­as­tat­ing dis­ease that has so far burned bil­lions of dol­lars in large­ly wast­ed re­search ef­forts.

ALS, or more for­mal­ly Amy­otroph­ic Lat­er­al Scle­ro­sis, has de­fied re­searchers for years now. The dis­ease first crip­ples and then typ­i­cal­ly kills its vic­tims in just a few years. Much of the work has been stymied by a fun­da­men­tal lack of un­der­stand­ing of what caus­es the dis­ease. But the two new­ly mint­ed biotech en­tre­pre­neurs say that they’re tak­ing two dif­fer­ent drugs and will look to ad­dress two dif­fer­ent man­i­fes­ta­tions of the dis­ease in an at­tempt to dis­rupt the crip­pling cas­cade of events that af­flicts pa­tients.

“We thought, why don’t we look with what we know is cor­re­lat­ing to pa­tients’ clin­i­cal de­cline,” says Klee. “In Alzheimer’s you lose neu­rons in your mem­o­ry cen­ter, the brain re­gions in­volved in mem­o­ry. The same in ALS, you lose neu­rons in the mo­tor cor­tex and spinal cord, and you lose move­ment abil­i­ty. The oth­er thing,” he adds, is that as neu­rons die, the brain im­mune sys­tem re­sponds and kills more neu­rons, caus­ing a tox­ic cy­cle that speeds the course of the dis­ease.

Amy­lyx is fo­cus­ing on the en­er­gy cri­sis in the mi­to­chon­dria and the un­fold­ed pro­tein prob­lem that caus­es a lot of the cell death, says Co­hen.

The two have honed in on a new treat­ment, AMX0035, that com­bines two drugs, sodi­um phenyl­bu­tyrate (PB) and tau­rour­sodeoxy­cholic acid (TUD­CA), aimed at tack­ling both those prob­lems at once. They have some clin­i­cal da­ta from ear­li­er stud­ies on both and enough back­ing now to test their idea that they can syn­er­gis­ti­cal­ly ad­dress ALS.

It’s a tall or­der con­cern­ing one of the Holy Grails of biotech R&D; some­thing akin to first-timer climbers tack­ling Mt. Ever­est on a shoe­string bud­get. But they say that the non­prof­it groups, es­pe­cial­ly in­volv­ing the hos­pi­tals like Mass Gen­er­al where the ex­pe­ri­enced in­ves­ti­ga­tors re­side, have made it all pos­si­ble with some key pric­ing breaks. And now, with some high pro­file con­nec­tions like Ter­meer, the vir­tu­al biotech with a staff of three full timers is start­ing out to see if they can get close to a peak that has elud­ed so many be­fore.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.

Social image: Shutterstock

Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.
The oral TKI, designed to zero in on HER2 with a bonus for penetrating the blood brain barrier, delivered a 46% hazard ratio — reduction in risk of disease progression or death — when combined with Herceptin and Xeloda compared to the branded combo alone. That was the primary endpoint. And then two key secondaries followed, starting with a 34% reduction in risk of death alone with a p value for overall survival that hit an approval worthy p=0.0048. There was a more dramatic 52% HR among almost half of the patients who had a brain metastasis at the time of the trial, which some of the analysts see as a key to market success.
We’ll have to wait until the San Antonio Breast Cancer Symposium for the breakdown on just how many months of PFS and OS Seattle Genetics is talking about.
While the researchers were after drug resistant third-line cases in the study, where regulators are generous in allowing high levels of toxicity for dying patients, the safety profile is still key here to the drug’s competitive position on the market. By steering clear of EGFR-linked toxicity, the company is looking for a better safety profile. And while the triplet led to a 5.7% drop out rate due to adverse events, compared to 3% for the double, analysts have been scoring this one much better than Nerlynx or Tykerb.

Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

FDA ap­proval lets Foamix set its maid­en ac­ne ther­a­py on course for US mar­ket launch

Months ago, Foamix leaned on its biggest shareholders — Perceptive Advisors and OrbiMed — to financially grease its wheels, ahead of the FDA decision date for its acne therapy. On Friday, that approval came in — and the topical formulation of the antibiotic minocycline is set for a January launch.

The therapy, Amzeeq (formerly known as FMX101), was approved to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients aged 9 and older.

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.

Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Christine Bunt, Robert Langer. Verseau

Armed with Langer tech and $50M, Verseau hails new check­point drugs un­leash­ing macrophages against can­cer

The rising popularity of CD47 has propelled the “don’t-eat-me” signal to household name status in the immuno-oncology world: By blocking that protein, the theory goes, one can stop cancer cells from fooling macrophages. But just as PD-(L)1 merely represents the most fruitful of all checkpoints regulating T cells, Verseau Therapeutics is convinced that CD47 is one of many regulators one can modulate to stir up or tame the immune system.

Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.

The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,500+ biopharma pros reading Endpoints daily — and it's free.