Tessera LLC

Vertex Pharmaceuticals signed a three-year deal with Orna Therapeutics to use the RNA biotech’s delivery particles to develop its next iteration of gene editing treatments for sickle cell disease and beta thalassemia. The partnership announcement comes just over a year after Vertex received the first approval for a gene-edited therapy for sickle cell disease and thalassemia known as Casgevy. Unlike Casgevy, where cells are edited outside the body and then reinfused back to the patient, Vertex’s goal here is to use Orna’s lipid nanoparticles (LNPs) — which are essentially spherical fatty acid shuttles — to deliver gene editors directly to the blood stem cells in a patient’s body. Vertex paid Orna $65 million, including an undisclosed amount in a convertible note. All in all, Orna could receive up to $635 million in milestones for the sickle cell and thalassemia programs. It could receive another $365 million related to up to 10 additional programs in other indications if Vertex opts in. Orna’s also eligible for tiered royalties on a potential product from this deal. “This [Orna’s LNP] technology, and the encouraging results the team has generated to date, offer a promising starting point for the discovery of LNPs to enable in vivo delivery of Vertex’s gene editing therapies,” a Vertex spokesperson told Endpoints News in an email. While the program is likely several years from human studies, the hope is that an in vivo gene editing therapy could be more straightforward to manufacture and could make obsolete the need for the grueling chemotherapy conditioning that is currently required to receive Casgevy as well as Lyfgenia and Zynteglo, which are sickle cell and beta thalassemia gene therapies marketed by bluebird bio. Both of those factors could also make such a therapy more accessible, where only a small fraction of sickle cell patients will be able to receive the currently approved gene therapies. Vertex is funding the three-year research partnership and has the option to extend it. The Vertex spokesperson wrote that the company has an internal research program for in vivo gene editing therapies and it is “pursuing multiple targets and approaches” for in vivo gene editing for sickle cell and beta thalassemia. The spokesperson did not say when the company expects to be entering human studies, saying that they would provide more details once they got closer to seeking regulatory clearance for clinical trials. One of the key bottlenecks in the gene editing field has been delivering gene editors outside of the liver. Lipid nanoparticles have been effective at delivering to the liver, but not beyond it. Researchers have been seeking new ways to deliver gene editors, including by attaching various targeting molecules to LNPs. However, Orna’s extrahepatic LNP doesn’t use added attachments. “These are all passive. These are not targeted. You don’t conjugate anything to the LNP,” Orna chief scientific officer Joe Bolen said. “It’s pretty flabbergasting, if you ask me, that we get really excellent non-hepatic delivery to various places.” Vertex said that Orna’s initial data demonstrated the passive delivery of LNPs to blood stem cells. But Bolen said the mechanism behind how Orna’s LNPs target beyond the liver hasn’t been determined and the company’s still investigating the details. In May, Orna and ReNAgade Therapeutics announced they were merging under the name Orna after both companies conducted layoffs amid a downturn in the genetic medicine industry. Following the merger, the company laid off more employees. Orna’s focus was developing therapies around circular RNA, while ReNAgade sought to develop RNA-based therapies with new lipid nanoparticles. The Vertex deal centers around the technology from ReNAgade — the startup generated a large barcoded library of LNPs that it infused “lot by lot,” in the words of Bolen, into non-human primates to study them. Others, including Tessera and Editas , are also pursuing in vivo gene editing for sickle cell disease. And in the near term, companies such as Vertex and its partner CRISPR Therapeutics, as well as Beam Therapeutics, are working to develop treatments that employ safer conditioning and could spare patients from harsh side effects of chemotherapy conditioning that include sores and infertility. Vertex is also researching small molecule approaches for sickle cell, according to its website.

SOMERVILLE, MA, USA I December 18, 2024 I Tessera Therapeutics, a biotechnology company pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, announced today that it has entered into an agreement with the Bill & Melinda Gates Foundation to jointly fund the company’s in vivo program for sickle cell disease (SCD). The funding includes an initial investment, with potential total investment of up to $50 million, from the Gates Foundation intended to support the development of Tessera’s SCD program into the clinic. The investment will support Tessera’s efforts towards advancing a SCD treatment and help further its objectives to develop transformative genetic medicines that are accessible globally. Tessera is developing Gene Writers TM for SCD designed to enable a true correction of the sickle mutation to wild-type with one-time intravenous administration in vivo , without the need for complex stem cell mobilization or toxic chemotherapy conditioning. Critical in enabling in vivo therapies, Tessera is leveraging its proprietary non-viral delivery platform to develop lipid nanoparticles targeting delivery of Gene Writers to long-term hematopoietic stem cells. “Sickle cell disease patients globally remain deeply underserved by existing treatment options. We are excited to develop what we believe will be a disruptive one-time curative treatment for SCD that is safer, easier, and more scalable than ex vivo genetic approaches,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “We look forward to advancing a genetic medicine that can potentially reshape the treatment landscape for sickle cell disease worldwide.” About Tessera Therapeutics Tessera Therapeutics is pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, with the aim to unlock broad new therapeutic frontiers. Our Gene Writing platform is designed to write therapeutic messages into the genome by efficiently changing single or multiple DNA base pairs, precisely correcting insertions or deletions, or adding exon-length sequences and whole genes. Our proprietary lipid nanoparticle delivery platform is designed to enable the in vivo delivery of RNA to targeted cell types. We believe our Gene Writing and delivery platforms will enable transformative genetic medicines to not only cure diseases that arise from errors in a single gene, but also modify inherited risk factors for common diseases and create engineered cells to treat cancer and potentially autoimmune and other diseases. Tessera Therapeutics was founded in 2018 by Flagship Pioneering, a life sciences innovation enterprise that conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. For more information about Tessera, please visit www.tesseratherapeutics.com. SOURCE: Tessera Therapeutics

Plus, news about Sensorion, Soleno Therapeutics, Corvus and Hansa Biopharma: Tessera Therapeutics bags up to $50M for sickle cell disease R&D: The investment is part of Tessera’s new agreement with the Bill & Melinda Gates Foundation to jointly fund development of an in vivo gene therapy for the rare blood disorder. The drugmaker is working on a one-shot treatment that doesn’t require patients to go through stem cell mobilization or chemotherapy conditioning. — Ayisha Sharma Tvardi Therapeutics makes a reverse merger and joins the Nasdaq: The company will use Cara Therapeutics as its shell in a deal expected to help get its STAT3 inhibitor through at least two Phase 2 readouts next year. Tvardi also secured $28 million in a separate private financing, while Cara sold off Korsuva to CSL Vifor for $900,000. — Max Gelman Sensorion’s gene therapy for deafness is safe in two patients: The company said administering SENS-501 via intra-cochlear injection along with minor surgery was well tolerated by the first two patients in the French biotech’s Phase 1/2 trial. There were no serious adverse events. On efficacy, Sensorion said “encouraging behavioral improvements” were observed. The trial will continue in patients aged 6 months to 31 months and who have congenital deafness linked to mutations in the gene for otoferlin. Recruitment should wrap up within the next six months. — Elizabeth Cairns Soleno Therapeutics secures up to $200M in debt financing: The Redwood City, CA-based biotech inked a loan and security agreement with Oxford Finance less than a month after the FDA delayed its decision on Soleno’s experimental Prader-Willi syndrome treatment. Soleno has drawn $50 million so far with the next $100 million to be available across three tranches if the treatment is approved. — Ayisha Sharma Corvus reports Phase 1 data for eczema drug: The drugmaker’s oral ITK inhibitor achieved a mean 55.9% reduction on the Eczema Area and Severity Index at 28 days compared with a 27% decline for placebo patients. There was just one treatment-related adverse event in the soquelitinib arm and it was low grade. Its stock $CRVS fell about 26% in premarket trading on Wednesday. — Ayisha Sharma Hansa Biopharma shares data for anti-IgG enzyme in Guillain-Barré syndrome: In an open-label Phase 2 study, a single dose of 0.25 mg of imlifidase plus intravenous immunoglobulin led to rapid overall improvement in the functional status of Guillain-Barré patients at 16 days. The Swedish company said patients started walking independently six weeks earlier than similar patients in a separate real-world study treated with immunoglobulin alone. They were also 6.4 times more likely to walk independently at week one, though only 4.2 times more likely at week four. — Elizabeth Cairns