Mammoth chief business officer and head of therapeutics Peter Nell

Bay­er jumps on board Mam­moth­'s ul­tra-small CRISPR tech with sights set first on the liv­er

Ger­man drug gi­ant Bay­er has looked to rein­vent it­self in re­cent years, mov­ing on from its past as a pri­mar­i­ly con­sumer health brand in­to one built around next-gen ther­a­pies. Now, Bay­er is tak­ing a fly­er on one of the chil­dren of CRISPR maven Jen­nifer Doud­na’s hal­lowed lab work­ing on tiny ver­sions of the gene edit­ing tech.

Bay­er will pay $40 mil­lion up­front and more than $1 bil­lion in po­ten­tial down­stream mile­stones for up to five in vi­vo gene edit­ing can­di­dates from Mam­moth Bio­sciences, a Doud­na lab spin­out de­vel­op­ing ul­tra-small en­zymes for eas­i­er pack­ag­ing and de­liv­ery in­to cells, the part­ners said Mon­day.

Mam­moth, which signed a sim­i­lar dis­cov­ery deal with Ver­tex late last year, is de­vel­op­ing CRISPR tools us­ing en­zymes rough­ly one-third the size of Cas9, the DNA scis­sors that helped make CRISPR fa­mous, to add or delete tar­get­ed genes through dou­ble-strand­ed breaks.

The com­pa­ny has de­vel­oped gene edit­ing sys­tems us­ing both Cas14 and Casɸ, among oth­er vari­ants, which are two small­er ver­sions that al­low for far greater flex­i­bil­i­ty in terms of de­liv­ery to tar­get tis­sues. That means Mam­moth’s team can push its ed­i­tors in­to small­er ade­no-as­so­ci­at­ed vi­ral vec­tors (AAV) but al­so in­to cer­tain lipid nanopar­ti­cles (LNP), the tech­nol­o­gy used to shut­tle the mR­NA-based Covid-19 vac­cines in­to cells, ac­cord­ing to ear­ly da­ta.

Ac­cord­ing to Mam­moth CSO Lu­cas Har­ring­ton, the pos­si­bil­i­ty of fit­ting more “pay­load” in­to de­liv­ery ve­hi­cles could help in­crease edit­ing ef­fi­cien­cy in cells, po­ten­tial­ly help­ing over­come cur­rent hur­dles for CRISPR tech.

For Bay­er, this deal comes a bit more than a year af­ter the Ger­man drug gi­ant, best known for its con­sumer health brand, ac­quired AskBio, an AAV-de­liv­ered gene ther­a­py com­pa­ny whose pick­up trum­pet­ed Bay­er’s move in­to next-gen ther­a­peu­tics and away from its staid phar­ma­ceu­ti­cal past. That biotech came aboard with ex­per­tise in build­ing a bet­ter AAV vec­tor, a puz­zle box tech­nol­o­gy with some safe­ty con­cerns that com­pa­nies all across the gene ther­a­py sec­tor are look­ing to solve.

Soon af­ter that pick­up, Bay­er an­nounced it would prop up a gene ther­a­py um­brel­la with­in its phar­ma­ceu­ti­cals busi­ness with the goal of adding a di­ver­si­fied set of modal­i­ties to dri­ve its next-gen push.

“Bay­er was re­al­ly look­ing for in vi­vo ap­pli­ca­tions, and I think our propo­si­tion is that small­er CRISPR sys­tems make this a per­fect com­bi­na­tion,” Pe­ter Nell, Mam­moth’s chief busi­ness of­fi­cer and head of ther­a­peu­tic strat­e­gy, told End­points News. “For us, it’s al­so how a com­pa­ny runs a busi­ness and what they know. You iden­ti­fy peo­ple who un­der­stand this and aren’t go­ing naive­ly in­to this.”

Al­though five tar­get ar­eas are part of the deal, the part­ners are on­ly say­ing now that the first tar­get on the list is the liv­er, a tis­sue most com­pa­nies be­lieve is the eas­i­est to hit. From there, the col­lab­o­ra­tion could run in any num­ber of di­rec­tions, which will be re­vealed at a lat­er date. Mean­while, Bay­er and Mam­moth plan to work to­geth­er on a nonex­clu­sive ba­sis lever­ag­ing the biotech’s ca­pa­bil­i­ties in ex vi­vo gene edit­ing, the same sort of tech­nol­o­gy used to craft off-the-shelf cell ther­a­pies.

Back in Oc­to­ber, Mam­moth signed a sim­i­lar li­cens­ing pact with Ver­tex worth $41 mil­lion up­front and $650 mil­lion in down­stream mile­stones for two ther­a­peu­tic ar­eas that weren’t dis­closed at the time of the an­nounce­ment. A month be­fore, Mam­moth an­nounced $195 mil­lion in new fund­ing (in­clud­ing a $150 mil­lion Se­ries D round and pre­vi­ous­ly unan­nounced $45 mil­lion Se­ries C).

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

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For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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