Hemophilia Gene Therapy Success & Biotech Funding Surge

A one-shot gene therapy for hemophilia A is superior to standard treatment, according to results from a phase 3 clinical trial.

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In this issue, a phase III clinical trial for a hemophilia gene therapy proves effective, STAT reporting brings back Michael Deem's involvement in the CRISPR baby fiasco, and a new synthetic biology company, called RootPath, launches with plans to make personalized T cell therapies. Plus: A slew of updates on synthetic biology funding.

Phase III Triumph

A one-shot gene therapy for hemophilia A is superior to standard treatment, according to results from a phase 3 clinical trial.

Hemophilia is a rare disorder in which blood loses its ability to clot. About 30,000 men in the U.S. are probably living with the condition, according to the CDC. The therapy was tested in 134 people, 112 of whom were followed up after one year.

There are three types of hemophilia: A, B and C. Type A is caused by a deficiency in a protein called factor VIII. Typical treatments are expensive and recurring, often entailing regular injections of clot-aiding compounds.

The gene therapy works like this: A piece of DNA, encoding the factor VIII protein, is packed inside of a virus. The virus is injected into the body, where it travels through the bloodstream. The viruses ultimately make their way to the liver, where they enters cells and coax them into producing a modified form of the factor VIII protein.

For this latest trial, men with severe hemophilia A each received a single infusion of the therapy, called valoctocogene roxaparvovec, at a dose of 6×1013 vector genomes per kilogram of body weight.

At week 49, the researchers measured factor VIII protein levels in the blood and tallied each participant's bleeding events. Every participant had at least one adverse event (38 percent had headaches, 37 percent had nausea) and 22 / 134 participants had a serious adverse event.

Still, with the new treatment, "one person receiving prophylactic factor infusions three times per week who has a response to gene therapy could avoid at least 150 intravenous infusions and have zero bleeds," according to an editorial in The New England Journal of Medicine.

Another 17 participants were followed for a second year. At the two-year mark, factor VIII levels had declined, which means researchers may need to consider how stable the treatment is, or whether additional infusions would be needed.

The therapy has already been granted Regenerative Medicine Advanced Therapy and Breakthrough Therapy designations from the Food and Drug Administration.

Read more in The New England Journal of Medicine.

A Deeper Look at Dr. Deem

Michael Deem was a professor at Rice University when He Jiankui announced that he had edited the genomes of twins in China, back in November 2018. The early surge of press didn't mention the professor, who advised He during the latter's graduate studies at Rice.

Deem quietly left his position at Rice in the summer of 2020, and a university investigation is ongoing. Now, a STAT investigation suggests "that Deem may have been involved more extensively than has previously been reported" in the CRISPR baby fiasco. "During the clinical trial in 2017 and 2018, Deem regularly received data about the research subjects, including sequence data of DNA pulled from the cells of the gene-edited children, according to a source with knowledge of the project," writes Megan Molteni. Lawyers for Deem have denied those claims.

Read more at STAT.

RootPath Launch

A new synthetic biology company, called RootPath, launched this week. The company is touting their ability to expedite "gene function interrogation by orders of magnitude," according to a press release. Based in Watertown, Massachusetts, RootPath is targeting personalized T-cell therapies for solid tumors, and is led by Xi Chen, who previously worked at Ultivue and did postdoctoral research at the Wyss Institute at Harvard University, where he worked on "DNA molecular programming in early cancer detection."

RootPath's core technology is called PathFinder DNA Assembly™. It's a method to auto-assemble "tens of thousands of inexpensive, short DNA fragments into thousands of long genes simultaneously." The method has already helped the company to screen "more than 20,000 [T-cell receptors] from tumor-infiltrating lymphocytes," many of which have anti-tumor activity.

Read more in the press release.

Money Talk

LanzaTech — a company harnessing microbes to capture emissions and convert them into chemicals — has teamed up with Twelve, a "fossil-free chemical company." Together, the teams are scaling technologies to convert carbon emissions into ethanol. Businesswire

LanzaTech will soon go public in a SPAC deal valued at $2.2 billion. It's the first carbon capture company to go public. City Index

Swedish firm, Ilya Pharma, raised €8.5M. The company is genetically engineering lactic acid bacteria to speed up wound healing. Labiotech

San Diego-based Codex DNA, a company selling a benchtop device to create synthetic DNA or mRNA from starting DNA templates, reported 59% year-over-year revenue growth. Codex DNA

Triumvira Immunologics, a clinical-stage company that develops engineered T-cell therapeutics for solid tumors, has raised $100M in a Series A round. Triumvira

Another company building T-cell therapies for solid tumors, called Affini-T Therapeutics, raised $175M in a round led by Vida Ventures and Leaps by Bayer. Businesswire

Massachusetts-based SQZ Biotechnologies has received a $2M grant from the National Institutes of Health to develop a "cell replacement therapy for Parkinson's Disease." The company uses cell engineering methods to "reprogram a patient’s own immune cells directly into dopamine-producing neurons." SQZ Biotech

Icosavax was developing a vaccine against SARS-CoV-2, called IVX-411, using synthetic biology methods. The interim results from a Phase 1/2 trial were a flop, though, and shares fell 20% on Friday. Market Watch

Briefly Noted

Two-photon holographic optogenetics can switch neurons on or off with pinpoint precision, thus "playing neurons like a piano," according to Rafael Yuste, professor of biology at Columbia University. The method improves upon traditional optogenetics in many ways. My latest for Spectrum.

Nucleate Dojo is launching a "bio builder house" in Boston, where early-stage founders aged 18 to 25 can live and work together from June through August 2022. Apply here. BioDojo

The U.S. Food and Drug Administration approved "CRISPR'd cows" for beef earlier this month. The new breed has slicker, shorter hair that helps the animals cope with hot weather. Modern Farmer

Octant, the therapeutics company using massively parallel techniques to design drugs, released version 2.0 of their Octopus system, which helps researchers rapidly sequence DNA plasmids. Octant

Eat Just is ramping up their cultivated meat manufacturing, breaking ground on a massive, $120M production facility in Singapore. Green Queen

London-based Ixaka has received an expanded patent to use its proprietary nanoparticle polymers for gene delivery applications. "The extended IP enables the development of therapies encapsulating any cargo including mRNA, plasmids and adenovirus associated virus (AAV), and gene editing technologies as well as lentiviral vector-based therapies," according to the press release. Ixaka

He Jiankui will likely be released from a Chinese prison this week, according to Science, but the desire to genetically edit embryos for medical applications remains a focus for many researchers. Science

On ABC News, geneticist Andrew Hessel talks about synthetic biology risks and challenges. ABC

AbSci, a company that designs therapeutic proteins using deep learning and synthetic biology, has announced a machine learning breakthrough for designing antibodies, in collaboration with NVIDIA. AbSci

For Grow by Ginkgo, journalist Max Levy interviews the authors behind the now infamous xenobot paper, in which cells taken from a frog worked together to perform tasks and then, ultimately, multiplied. Grow

Come 'n' Go

Mammoth Biosciences, the gene editing spin-out from Jennifer Doudna's lab at UC Berkeley, appointed Elaine Sun as Chief Operating Officer and Chief Financial Officer, Ted Tisch as Chief Agility Officer, and announced two new vice presidents, including Dimitrois Zisoulis as VP for Genome Engineering. Sun has previously worked with Cirius Therapeutics and Dynavax. Businesswire

Cemvita Factory, a company using synthetic biology to "reverse climate change," according to their site, expanded its leadership team. They appointed a new Chief Business Officer, Chief Commercial Officer, and Head of Strain Development, and doubled the size of their Houston-based laboratory. Cemvita

Until next time,

— Niko // @NikoMcCarty // niko@codonmag.com

Correction: An earlier version of this newsletter said that there are two types of hemophilia. There are three types.