Lachlan MacKinnon (L) and Adrian Woolfson (Replay)

With AAV al­ter­na­tive and DNA writ­ing tech, a new hub-and-spoke start­up wants to ‘de­moc­ra­tize’ gene ther­a­pies

When Adri­an Woolf­son was head of R&D at Sang­amo, he be­gan con­tem­plat­ing start­ing his own com­pa­ny. His goal? Solve some of the key chal­lenges plagu­ing ge­nom­ic med­i­cine he’d seen while work­ing on a wide spec­trum of Sang­amo’s pro­grams.

Then, he met Lach­lan MacK­in­non, a biotech in­vestor, in Lon­don, and the two re­al­ized they shared a sim­i­lar vi­sion, de­spite their “or­thog­o­nal” back­grounds, he told End­points News.

Re­play, their new hub-and-spoke start­up, looks to change the way gene ther­a­pies are made. With $55 mil­lion in seed mon­ey, the biotech has col­lect­ed a se­ries of plat­forms, in­clud­ing an HSV vec­tor, pro­tein rewrit­ing al­go­rithm and a DNA writ­ing tool from George Church’s lab.

“We iden­ti­fied es­sen­tial­ly three key chal­lenges that we’re solv­ing for, which we think will de­fine the fu­ture,” Woolf­son, who is the chair­man and pres­i­dent, said. “The first of those is pay­load ca­pac­i­ty; the sec­ond is the need for an off-the-shelf, low cost scal­able, and ex­ten­sive­ly ge­nom­ic en­gi­neered cell ther­a­py plat­form; and the third is the abil­i­ty to as­sem­ble big DNA.”

Re­play’s pri­ma­ry tech­nol­o­gy is its HSV de­liv­ery sys­tem. While AAV vec­tors can gen­er­al­ly on­ly hold about 4.7 kilo­bas­es of a gene, HSV vec­tors can hold about 150 kilo­bas­es. With that in­creased ca­pac­i­ty, ther­a­pies us­ing the vi­ral vec­tor could ex­tend to dis­eases with big­ger genes, like mus­cu­lar dy­s­tro­phy, and genes with their in­trons (and reg­u­la­to­ry parts) in­tact, Woolf­son not­ed.

Woolf­son added Re­play has two class­es of HSV vec­tors. “We’ve got our gene-delet­ed HSV, but we’ve al­so got what we call an am­pli­con — which is an HSV in which we’ve stripped out vir­tu­al­ly all of the genes — and this is al­most a non-vi­ral vec­tor,” Woolf­son said. “And we think that will ac­tu­al­ly be prob­a­bly the most com­pelling of all.”

How­ev­er, the ju­ry re­mains out on whether an HSV-based ther­a­py will be safer than the stan­dard AAV, as the vi­ral vec­tor trig­gers a dan­ger­ous im­mune re­sponse. Woolf­son ac­knowl­edged that like for AAV, the body has neu­tral­iz­ing an­ti­bod­ies against HSV, though he added that HSV has evolved to bet­ter evade the im­mune sys­tem.

A suite of biotechs has grown out of the ef­fort to solve the var­i­ous prob­lems re­lat­ed to gene ther­a­pies. Splice­Bio is try­ing to solve the pay­load lim­i­ta­tion through pro­tein splic­ing, and Aper­tu­ra is work­ing on cus­tom-de­signed AAV vec­tors that it hopes can get AAVs to dif­fi­cult-to-ac­cess ar­eas.

Re­play has al­so li­censed a DNA writ­ing tech­nol­o­gy, used for build­ing syn­thet­ic strands of DNA. “We think we can re­ca­pit­u­late what we’re see­ing with DNA se­quenc­ing and dra­mat­i­cal­ly bring down the cost of writ­ing to help to pi­o­neer a new era of genome writ­ing,” Woolf­son said.

So far, the plat­form com­pa­ny has spun out five dif­fer­ent prod­uct com­pa­nies — four HSV gene ther­a­py com­pa­nies fo­cused on mono­genic dis­or­ders, in­clud­ing one for Parkin­son’s and one for Duchenne mus­cu­lar dy­s­tro­phy, and one en­zyme writ­ing com­pa­ny.

Re­play’s seed round was led by KKR and OMX Ven­tures, and al­so in­clud­ed AR­TIS Ven­tures and Lans­downe Part­ners, SALT, DeciBio Ven­tures, and Ax­i­al.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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Albert Bourla, Pfizer CEO (Efren Landaos/Sipa USA/Sipa via AP Images)

Pfiz­er makes an­oth­er bil­lion-dol­lar in­vest­ment in Eu­rope and ex­pands again in Michi­gan

Pfizer is continuing its run of manufacturing site expansions with two new large investments in the US and Europe.

The New York-based pharma giant’s site in Kalamazoo, MI, has seen a lot of attention over the past year. As a major piece of the manufacturing network for Covid-19 vaccines and antivirals, Pfizer is gearing up to place more money into the site. Pfizer announced it will place $750 million into the facility, mainly to establish “modular aseptic processing” (MAP) production and create around 300 jobs at the site.

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Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Yuling Li, Innoforce CEO

In­no­force opens new man­u­fac­tur­ing site in Chi­na

Innoforce is off to the races at its new site in the city of Hangzhou, China.

The Chinese CDMO announced last week that it has started manufacturing at the new facility, which was built to offer process development and manufacturing operations for RNA, plasmid DNA, viral vectors and other cell therapeutics. It will also serve as Innoforce’s corporate HQ.

The company said it’s investing more than $200 million in the 550,000-square-foot manufacturing base for advanced therapies. The GMP manufacturing facility features space for producing plasmids with three 30-liter bioreactors. For viral vector manufacturing, Innoforce also has 200- and 500-liter bioreactors at its disposal, along with eight suites to make cell therapies. The site also includes several labs and warehouse spaces.

Vas Narasimhan, Novartis CEO (Thibault Camus/AP Images, Pool)

No­var­tis bol­sters Plu­vic­to's case in prostate can­cer with PhI­II re­sults

The prognosis is poor for metastatic castration-resistant prostate cancer (mCRPC) patients. Novartis wants to change that by making its recently approved Pluvicto available to patients earlier in their course of treatment.

The Swiss pharma giant unveiled Phase III results Monday suggesting that Pluvicto was able to halt disease progression in certain prostate cancer patients when administered after androgen-receptor pathway inhibitor (ARPI) therapy, but without prior taxane-based chemotherapy. The drug is currently approved for patients after they’ve received both ARPI and chemo.

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Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

The first generation of personalized CAR-T therapies made big waves in the treatment of lymphoma for their stunning efficacy. Nkarta is hoping its off-the-shelf natural killer cell approach will stand out on safety — while keeping some of those impressive numbers on responses.

In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.

Pfiz­er-backed Me­di­ar Ther­a­peu­tics ropes in an­oth­er Big Phar­ma in­vestor

A biotech centered on treating fibrosis — born out of Mass General and Brigham and Women’s Hospital — has received a financial boost.

According to an SEC filing, the company has raised $31,761,186 in its latest funding round, which includes 17 investors. The filing lists six names attached to the company, including Meredith Fisher, a partner at Mass General Brigham Ventures and Mediar’s acting CEO.

Ken Greenberg, SonoThera CEO

Gene ther­a­py goes acoustic as ARCH-backed biotech launch­es with ul­tra­sound gene de­liv­ery plat­form

After co-founding two biotechs off virus-based therapies, one for pain and one for cancer, Ken Greenberg decided to go in a different direction for his newest biotech, SonoThera.

Based out of San Francisco, SonoThera announced Monday morning that it raised $60.75 million to develop new gene therapies — but delivered by ultrasound, which Greenberg says can address the major challenges facing more conventional viral gene therapies.

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