TWEAK

Graphite entered into a license and option agreement with an undisclosed third party in August Matthew Porteus, M.D., Ph.D., is trying to write another chapter for his sickle cell disease project. Three years after Graphite Bio launched to build on his work, Porteus has struck a deal to save the floundering project and advance deeper into the clinic under a new biotech. Porteus studied the use of CRISPR to correct the mutation that drives sickle cell at his Stanford University lab. The studies led to Graphite, which listed Porteus as a scientific founder when it emerged with a $45 million series A round in 2020. Graphite’s story quickly took a dark turn, with the biotech seeing a serious adverse event in the first patient it dosed and halting development of the candidate weeks later. Those events marked the beginning of the end for Graphite, which went from raising a $238 million IPO to entering into a reverse merger in less than 30 months. But Porteus has given the sickle cell program a chance of outliving the biotech that first tried to bring it to market. The Stanford professor has co-founded a new biotech, Kamau Therapeutics, to emerge from the ashes of Graphite. Kamau “received an option to acquire all genome editing assets” through a “strategic transaction with Graphite.” The newly minted biotech plans to study the sickle cell asset, nulabeglogene autogedtemcel (nula-cel), that Graphite walked away from in the wake of the adverse event. Investigators have now tracked the patient who received nula-cel for one year. Ahead of the release of the one-year data Monday, Kamau shared a look at six-month results, identifying “lower-than-expected cell survival rate, necessitating platelet and red blood cell transfusions due to low platelet counts” as a problem and fingering eltrombopag as the cause of the adverse event. Eltrombopag is used to treat low platelets in the blood and was not initially part of the trial protocol.  The findings have informed a focus on manufacturing. Kamau is working with an outsourcing partner to increase cell yield and improve overall cell health. The goal is to establish a more robust manufacturing framework. Graphite entered into a license and option agreement with an undisclosed third party in August. Under the terms of the deal, the third party secured an option on nula-cel and related assets and gave Graphite a 20% stake in its business. The option was contingent on the timely achievement of “a financing milestone” by the third party. Graphite’s last update described a tweak it made to the agreement in September. Meanwhile, what's left of Graphite folded into vision-loss biotech LENZ Therapeutics in November. 

With a name like Pretzel Therapeutics, some may think the fledgling biotechnology company specializes in baking.The startup, officially launched Monday by a trio of European mitochondrial biology researchers, is instead looking at rare genetic disorders and diseases of aging such as Alzheimers and Parkinsons.With $72.5 million in Series A funding, Pretzel plans to advance more than five research programs using technologies that involve gene editing as well as control mitochondrial gene expression and health.Pretzels name was inspired by the shape of mitochondria, which resembles the twists of the German bread.A mitochondrion supplies cells with the power they need to survive. They turn the energy the body gets from food into fuel that cells use for a variety of chemical reactions.When their DNA, or mtDNA, mutates in certain ways, mitochondria produce less energy, preventing cells from functioning properly. Mitochondrial dysfunction is the cause of dozens of rare genetic diseases, and is thought to be a factor in common age-related disorders such as Alzheimer's.Pretzels scientists aim to use gene editing to remove mutated mtDNA that other genome manipulation techniques such as CRISPR cant reach because of the organelles tiny size, said Jay Parrish, Pretzels CEO.The company also hopes to control mitochondrial genome expression by targeting with small molecule drugs the enzymes involved in mtDNA replication, transcription and translation. Small molecule drugs might also be used to tweak the mitochondrias systems for quality control.A handful of other companies are focused on mitochondrial diseases. Stealth BioTherapeutics, which until recently traded under the stock ticker MITO, is one of the most advanced, with a drug candidate in late-stage testing. But its hit several significant setbacks, falling short in a previous Phase 3 study and getting a drug application rejected by the Food and Drug Administration.Elsewhere, Mitobridge, a biotech bought by Astellas in 2017, is in clinical testing with two drugs. Vincere Biosciences is researching small molecules to improve mitochondrial quality, while Reneo Pharmaceuticals is developing drugs to treat rare genetic diseases caused by mitochondrial dysfunction.But Pretzel claims it is looking at mitochondrial disease more broadly than others in the field.People have been working with the mitochondria for a long time but this is a different approach, Parrish said. The mitochondria itself is an amazing organelle that does all these cool things beyond just energy production. There are drugs that hit it, but it has untapped potential.The company will consider raising another round of private funding in one to two years, but Parrish declined to say when it expects to advance a drug into the clinic. By then, Pretzel also hopes to have begun research on how its platform can treat diseases that arent directly caused by mitochondrial dysfunction, such as rare cancers.Arch Venture Partners and Mubadala Capital first began building Pretzel in early 2020, aiming to create a platform biotech company. Then, Paul Thurk, the Arch partner leading the project, suddenly died in January 2021.Three investors Parrish, Arch managing director Kristina Burow and Mubadala executive director Alaa Halawa forged on with the project in honor of Thurk.We were able to recover due to the team who are not just great scientists or great investors, but really great people, said Gabriel Martinez, one of Pretzels directors.Pretzel will be based in Waltham, Mass. with a research facility in Gothenburg, Sweden.Arch and Mubadala, a sovereign venture capital fund from the United Arab Emirates, invested $15 million apiece in the company. GV, Invus and Angelini Ventures filled out the round along with more than half a dozen other investors.Though Pretzel isn't disclosing exactly which diseases its targeting, its investors see a wide range of possibilities.Were more intrigued and excited by the hard-to-reach fruits like Alzheimer's and diabetes, which we believe this company is poised to address, Halawa said. '