#322: In-Vivo Gene Editing Research Demonstrates Progress Toward A Treatment For Hereditary Polyneuropathy, & More

Intellia Therapeutics (NTLA) and Regeneron Phamaceuticals (REGN) made history at last year’s Peripheral Nerve Society Conference when they presented the world’s first data on CRISPR Cas9-based in-vivo gene editing therapy in patients with Hereditary Transthyretin Amyloidosis (hATTR) polyneuropathy¹. hATTR is a disease in which amyloid proteins build up and, if untreated, can cause the failure of multiple organs, typically the heart and nerves. Notably, the researchers demonstrated that editing the TTR gene could deliver a one-time treatment that reduces sustained serum TTR, eliminating the need for chronic therapy.

This week, the same researchers shared new, interim data from their ongoing Phase I study of fifteen ATTRv-PN² patients who were treated across four dose cohorts. Those patients showed sustained serum TTR reductions at all doses, with the first cohort reaching twelve months. Notably, at six months the mean TTR reduction for the highest dose cohort was still at 93%.

Although the sample size was small, sustained serum TTR reductions potentially indicate that this could be a one-time therapy to cure ATTRv-PN patients.

[1] The results of the milestone trial were published in the New England Journal of Medicine.

[2] ATTR amyloidosis with polyneuropathy (ATTRv-PN).

In the third Defi bridge hack since February, thieves made off with $100 million after gaining access to a 2-of-5 multi-signature wallet that controlled the Horizon Bridge protocol connecting Ethereum to the Harmony blockchain. The hack resembled the Ronin Bridge hack which compromised a 5-of-9 multi-signature wallet and stole ~$620 million in late March. Added to the $323 million Wormhole Bridge hack in February, the Horizon attack pushed the total stolen from cross-chain bridges to more than $1 billion thus far this year.

While multi-signature wallets distribute across multiple parties the risk of private key compromises, the recent hacks illustrate that 2-of-5 and 5-of-9 schemes³ do not adequately protect the hundreds of millions of dollars bridged between public blockchains. Bridges like Ronin, in which one party controlled four of the nine keys, are particularly vulnerable.

Nevertheless, the desire to move value across public blockchains remains astonishingly high. The team behind the Ronin bridge that powers play-to-earn game Axie Infinity recently announced that it has reimbursed victims of the hack, in part with a $150 funding round in April led by Binance, and that it will resume operations this week.

Blockchain ecosystems focused on interoperability, like Polkadot and Cosmos, could benefit from the weakness in trusted bridges. These networks seek to leverage shared security models that securely permit assets and messages to move across compatible chains––without the need for trusted intermediaries or traditional bridges.

[3] Multi-signature wallets require multiple parties to approve (i.e., sign) a transaction. For example, a 2-of-5 multi-signature wallet requires two signatures from among the five parties.

This week, Cruise became the first self-driving ride-hail service to receive a permit to charge for fully autonomous rides in San Francisco. Majority-owned by General Motors, Cruise is undercutting Uber’s prices by about 15%, though its rides are limited to 30 miles per hour (mph) during the night from 10pm to 6am.

ARK’s research suggests that autonomous ride-hail services could operate at-scale profitably with prices as low as $0.25 per mile, a level that may not be necessary based on how consumers value their time. According to our research, price points in the $0.60-$1.00 per mile range should stimulate significant demand. At $6-7 per mile, Cruise’s prices are significantly higher, giving it the latitude to drive demand with lower prices.

GM’s CEO, Mary Barra, has suggested that rides could cost less than $1 per mile in the long run, and former Cruise CEO, Dan Ammann, suggested the that its revenues could scale to $50 billion by 2030. To lower costs, we believe Cruise must increase its vehicle utilization rates, which will depend not only on a daytime permit but also on scaling autonomous car units to a level high enough to minimize passenger wait times.