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Seven years ago, Daniel Ives believed that he was on the cusp of solving aging. He wanted to continue working on a discovery he made as a graduate student at the University of Cambridge, but couldn’t get support to continue the research as a postdoc. So he decided to go it alone. “I just spent money out of my own bank account on life science experiments, which are incredibly expensive, and you run out of money very quickly, so I roped in family,” Ives told Endpoints News in an interview. “I got a few donations, and eventually I asked my girlfriend, ‘Will you give me your life savings for the next experiment?’” She said “no” and told Ives to talk to real investors. It was good advice. Since then, Ives has raised $18 million for his startup Shift Bioscience, including a newly disclosed $16 million seed funding, he told Endpoints exclusively. BGF, a firm that invests in British and Irish companies, led the funding. Returning investors include F-Prime Capital, Kindred Capital and Jonathan Milner, the founder and former CEO of Abcam. Shift Bio is set on finding drugs that rewind the epigenetic clock. The clock is a tool to estimate a person’s age by looking at chemical markers on their DNA, and many scientists in the anti-aging field believe that reversing the clock is a prerequisite for improving healthy longevity. The startup’s early work shows just how much stock researchers put in the clock. Ives was initially focused on mitochondria, the power plants of the cell. They can accumulate mutations with age, hindering their energy output yet causing them to replicate faster like cancer. Ives found a way to help healthy mitochondria flourish and outcompete renegade ones in rapidly aging mice. The treatment relieved some of their symptoms, and the mice looked younger, but their epigenetic clocks didn’t budge. After repeating the experiment in naturally aged animals, with similarly disappointing results, Ives ditched the approach. “If we’re really going to translate this to people for physiological aging, for you and me, not just some mouse, we’ve got to make sure this clock moves,” Ives said. “Once we’ve got that, we can pair it with functional data.” The failure inspired him to pursue an even bigger goal: to find genes that control the epigenetic clock and use them to reverse aging. Researchers have been rewinding the epigenetic clock in a petri dish for nearly two decades, but finding a way to do it in humans is proving challenging. A cocktail of four proteins called Yamanaka factors can turn a cell from an adult — even a centenarian — into a stem cell with an epigenetic age of zero. The blank slate cell can be turned into other useful cells in the lab. But when this process is replicated directly in a mouse, the animals develop tumors composed of a potpourri of tissues. “It’s like a body without a body plan,” Ives said. “It’s clearly something very dangerous from a therapeutic perspective.” At Shift Bio, he is trying to find ways to rejuvenate cells, making them healthy and spry, without causing them to lose their identities. “We want to rewind the clock, but we don’t want to rewind development,” he said. To do that, his startup collected cells with as many epigenetic ages as he could find. The company used single-cell RNA sequencing to record which genes are turned on in the cells and methylome sequencing to look at their epigenetic markers. Machine learning helped them connect the two datasets and predict age based on gene expression. Shift Bio has also used the data to develop an AI cell simulation, allowing its researchers to probe different genes on a computer and predict how they affect the clock before committing to lab experiments. It’s helped the company discover six new ways of rejuvenating cells, none of which involve the four Yamanaka factors, Ives said. He won’t name the genes involved, but said one of the approaches seemed so simple that he was shocked that someone else hadn’t already discovered it. “These simulations are like a new telescope on biology and allow us to explore combinatorial space, and we’re able to find things for the first time,” Ives said. Ives plans to use the new funding to make sure that the rejuvenation approaches it found are broadly applicable to many cells in the body, which is vital for a “disease-agnostic approach.” The startup has recently grown from just eight employees to nearly 20, and a big focus of the new team will be thinking about how to turn some of its discoveries into medicines. The genes that the startup has identified so far are all transcription factors, which are notoriously difficult starting points for drug discovery. Shift Bio will face competition. Another startup, clock.bio, recently said it had discovered 140 genes vital to cell rejuvenation . Shift’s biggest competitor, Altos Labs, launched with $3 billion in early 2022 and a star-studded scientific team that included Steve Horvath, the biologist who discovered the epigenetic clock, and his collaborator Ken Raj, who was trying to understand the biological basis of the clock. But Ives is undaunted and feels that the well-funded and secretive Altos only helps his cause. “By attracting all that credibility to the field, it became easier for us to attract investors,” he said. “It’s such a long road, the risks are so high, it’s going to be amazing if anybody pulls this off.”

The company’s single-cell-based discovery engine can detect the specific pathogenic cells that cause disease, and their surface markers. Credit: PeopleImages.com – Yuri A/Shutterstock. Arda Therapeutics has secured $43m in Series A financing to develop targeted cell depletion therapies. Andreessen Horowitz (a16z Bio + Health) spearheaded the investment round with contributions from a consortium of investors including Two Sigma Ventures, RV Invest, Eli Lilly and Company, GV and Biovision Ventures. The company is focused on eliminating the cells responsible for disease, rather than simply modulating the proteins they produce. Its advanced single-cell-based discovery engine plays a crucial role in detecting the specific pathogenic cells that cause disease and their surface markers with remarkable precision. This novel method paves the way to create targeted biologics that can selectively eradicate harmful cells, thereby preserving healthy tissue. See Also: South Korean company Dong-A ST wins FDA approval for Stelara biosimilar Roche wins first-line approval for PI3K inhibitor combo in breast cancer The potential benefits of this approach include significantly improved efficacy and reduced side effects when compared to traditional treatments. Arda’s technology could potentially treat a range of conditions including fibrotic diseases such as pulmonary fibrosis, and autoimmune and metabolic disorders. Arda Therapeutics founder and CEO Adam Freund stated: “Arda is at the forefront of a paradigm shift in treating chronic diseases. “By focusing on the cells at the core of disease, we can develop therapies that are not only more effective, but also have the potential to fundamentally change patient outcomes. With drug approval rates declining and efficacy improvements stalling, Arda’s strategy to target cells — not pathways — offers a transformative shift in how chronic diseases are treated. With the support of our Series A investors, Arda is well-positioned to progress our lead programmes toward the clinic and expand our platform to tackle even more disease areas.” In conjunction with the funding announcement, Arda also appointed Scott Turner as its new chief scientific officer. Turner stated: “I’m thrilled to be joining Arda at such an exciting time. “The team has built an impressive platform for targeting pathogenic cells with precision, which holds tremendous potential for addressing the unmet needs in chronic disease. “I look forward to working closely with the team to advance our lead programmes toward the clinic and develop innovative therapies that can make a meaningful impact on patients’ lives.”

Last August, stem cell biologist and bit.bio founder Mark Kotter launched a new startup with an ambitious goal: within a year, to identify every gene that plays a role in restoring or repairing aging cells. That company, called clock.bio, says it has identified a list of 140 genes that it calls the “Atlas of Rejuvenation Factors.” The startup isn’t naming any of the genes yet, but it’s going through them one by one to come up with the top 10 that it believes will make good drug targets. “We see a couple of genes that you would expect,” Markus Gstöttner, who was appointed CEO of clock.bio in March, told Endpoints News in an exclusive interview. “Then there are other genes that are kind of much less well understood, and on all of them, we want to understand how the pathways work at a cellular level.” Gstöttner, who co-founded the lab-grown meat startup Meatable with Kotter in 2018, said that clock.bio views itself as a “faster, smaller, more nimble” competitor to Altos Labs, the anti-aging biotech that launched with $3 billion in 2022 and a focus on “cellular rejuvenation programming.” In contrast, clock.bio launched with a modest $4 million in a pre-seed round last year and recently raised an additional $5.3 million in its seed funding. The round was led by London venture capital firm LocalGlobe. Other investors include BlueYard Capital, Onsight Ventures and Abcam founder Jonathan Milner. Some of the money has already gone to massive CRISPR screens and single-cell RNA sequencing experiments on more than three million stem cells. The company says it forcibly ages stem cells and then uses gene editing to activate or inhibit genes to find ones that promote or prevent rejuvenation. Gstöttner said that one-quarter of the 140 genes promote rejuvenation when activated. But the company is actually more excited about the other 75% of genes that promote rejuvenation when they are knocked out. That’s “good news,” Gstöttner said, since inhibiting genes or the proteins they encode is a far easier task. Last year, Kotter told Endpoints that a comprehensive screen of the human genome would rapidly lead to ideas for new drugs that could extend human healthspan, the amount of time we live free from the diseases of aging, by two decades. That extension will be measured with molecular clocks, tests that rely on changes to epigenetic markers, gene expression or certain genetic sequences to estimate a person’s age. But proving that these biomarker changes are linked to better health outcomes could prove tricky. Like other biotechs that have been treading into the anti-aging territory, clock.bio will likely need to assess more traditional clinical endpoints in specific diseases to appease regulators. Clock.bio has set the goal of starting a Phase 3 clinical trial by 2030. That tight timeline will likely require the company to find existing small molecule compounds, either approved or still-experimental drugs, that can rapidly move through animal testing and into the clinic. Gstöttner said that in addition to advancing its own pipeline of repurposed drugs, he will look for pharma partners to create new drugs for some of the startup’s most promising rejuvenation genes. The partnership hunt and a Series A fundraise will begin in earnest next year.