Semma Therapeutics, Inc.

Boston biotech Axonis Therapeutics has raised a $115 million Series A to test whether its oral drug AXN-027 can help patients with focal epilepsy and diabetic neuropathic pain. The financing, disclosed Wednesday morning, will get the biotech into the clinic around the end of this year, or about the same time Ovid Therapeutics expects to begin human trials with a similar approach by way of an AstraZeneca platform it licensed. Both companies are looking at KCC2, a CNS chloride transporter that is key to electrical signaling in the brain. KCC2 allows for neuronal GABA signaling. The GABA pathway has been targeted by multiple drugmakers , including Sage’s postpartum depression medicine Zurzuvae , but biotechs have yet to enter the clinic with a focus on KCC2, CEO Joanna Stanicka told Endpoints News . “Often GABA treatments can induce global inhibition, which leads to this cognitive impairment and sedation often reported by patients,” Stanicka said, adding that focused inhibition should avoid those side effects. The 13-employee biotech also said Wednesday that it added Donald Manning as chief medical officer and Jeff Imbaro as operating chief. Manning previously held the same post at Travecta, Pacira BioSciences and Adynxx. Imbaro was in the same role at stroke-focused Elevian, and before that he was a founding member of Vertex-acquired Semma Therapeutics. Axonis was founded by spinal cord injury patient advocate and board observer Bob Yant about 15 years ago, but it didn’t become “operational” until 2019, Stanicka said. Prior to the Series A, Axonis had raised about $34 million in seed funding and about $9 million in government and foundation money, Stanicka said. Its investors include Cormorant Asset Management, venBio, Sofinnova Investments, Merck’s corporate venture arm and others. The startup anticipates the Series A will fund AXN-027 through Phase 2 proof-of-concept studies, she said.

Stem cell biologist William Rust has been quietly working on a cure for diabetes for more than a decade. Later this year, surgeons will implant his company’s pancreatic organoids in people with type 1 diabetes in hopes of restoring their ability to make insulin, Rust told Endpoints News in an interview. Rust’s company, Seraxis, recently received authorization from the FDA to begin the trial. The Germantown, MD-based biotech will recruit six to nine people with type 1 diabetes and severe hypoglycemia. Rust expects to have the first glimpse of whether the approach is working early next year. “The output is easy to measure. Either they have insulin in their blood, or they don’t,” Rust said. The therapy is made from pancreatic stem cells derived from the organ of a single donor collected several years ago. It’s the latest addition to a small but growing number of efforts centered on using stem cells to grow pancreatic islets that could possibly cure diabetes. Vertex Pharmaceuticals, the leader of the pack, drew attention from doctors with its experimental islet cell therapy that reduced or eliminated the need for insulin injections in nearly a dozen patients in its ongoing clinical trial. Eli Lilly and Novo Nordisk, the biggest sellers of insulin, are also in the early stages of designing their own stem cell-derived therapies. Seraxis has kept a relatively low profile in the field. Rust founded the company in 2013 and survived on about $10 million from two small rounds of funding before landing a $40 million Series C financing in 2021 from Eli Lilly, Frazier Healthcare Partners, Polaris Ventures and T1D Fund. The clinical trial clearance triggered the third tranche of that financing, worth $14 million, Rust said. Seraxis was born out of Rust’s frustration with the field’s fixation on embryonic stem cells. In the 2000s, these cells held promise to grow human tissues in the lab or replace them directly in the body. But their very ability to turn into any cell of the body also made them hard to control. “It was very difficult to convince them to become just one cell type,” Rust said. “They could make those cells, but only in small proportions. It was hard to imagine making a product out of that.” Some scientists, including Harvard biologist Douglas Melton, have found ways to make insulin-secreting beta cells using stem cells originally derived from a single human embryo. That research became the basis of Melton’s biotech company Semma Therapeutics, which Vertex bought for $950 million in 2019. But well before that acquisition, Rust was working on his own method that would use a single human pancreas as the starting point. At Seraxis, he found a way to take those adult cells and partially rewind their development to create a pancreas stem cell line. Rust claims the approach is more efficient, with fewer unwanted cells arising during manufacturing than the embryo-derived approach. He even shared the company’s cells with Lilly scientists and T1D Fund’s academic partners to evaluate in their own labs, before locking down the $40 million financing in 2021. “We couldn’t do anything on reputation alone,” Rust said. While Vertex infuses its islet cells into the liver, where they embed themselves in the organ, Seraxis plans to implant the islets into the omentum, a flap of fatty tissue neighboring the stomach. A small number of people with type 1 diabetes have had pancreatic islets implanted from cadavers into their omentum. “We piggybacked on that idea,” Rust said. “We can monitor it by regular medical imaging, and if there is ever a problem, you can remove it with simple resection, just snip it off.” Patients will have to take immunosuppressants to prevent the immune system from destroying the islets. Seraxis is also developing a second cell line that is gene-edited to remove proteins that expose the cell’s foreign identity to the immune system. If all goes well, a clinical study of that approach could begin in 2026. Rust said the company’s funding will last through 2025, long enough to get data from its first clinical trial. If the results are positive, he will start raising a crossover round to fund bigger studies as well as an initial trial of the gene-edited therapy. “The next steps will be much more expensive,” Rust said. “And right now, the winds seem to be pushing us to IPO.”

NEW YORK, June 25, 2024 /PRNewswire/ -- Breakthrough T1D, formerly JDRF, the leading global type 1 diabetes (T1D) research and advocacy organization, gathered with researchers, diabetes professionals, and other leaders in T1D at the American Diabetes Association's (ADA) 84th Scientific Sessions, where Breakthrough T1D scientists, clinicians, and Breakthrough T1D-funded researchers presented research results that will improve outcomes for people with T1D. Held June 21-24 in Orlando, Florida, the ADA Scientific Sessions is one of the largest diabetes conferences in the world. Breakthrough T1D-supported research has been highlighted at this annual event since the organization started funding research in the 1970s. This year, researchers presented more than 180 studies—with Breakthrough T1D funding at present or in the past—that are paving the way for more life-changing T1D breakthroughs. "As we drive toward cures, Breakthrough T1D connects and funds the brightest minds to help accelerate cures, advance treatments, and improve access to care for those who live with type 1 diabetes all over the world. The research presented at the ADA Scientific Sessions demonstrates the incredible progress being made in the space," said Aaron Kowalski, Ph.D., Breakthrough T1D CEO. "Breakthrough T1D is thrilled to lead and support the innovation and cutting-edge research that are accelerating life-changing breakthroughs for people with type 1 diabetes." A key highlight of this year's conference was the presentation and publication of the first-ever international consensus guidance for monitoring early-stage T1D. Convened and led by Breakthrough T1D, the guidance was developed in conjunction with over 60 international experts representing 10 countries and endorsed by 11 national and international organizations and societies. It provides guidance for monitoring children, adolescents, and adults who test positive for T1D autoantibodies, along with recommended frequencies of monitoring and actions for health care professionals when risk of progression towards symptomatic T1D is high. Notably, the guidance also includes recommendations for educational and psychosocial support. "Early detection of type 1 diabetes is a priority for Breakthrough T1D, and the development of this guidance provides clarity and next steps for individuals, caregivers, and health care professionals following a positive autoantibody test," said Sanjoy Dutta, Ph.D., Breakthrough T1D chief scientific officer. "Clear monitoring guidance create a pathway to realize the benefits of early detection of T1D, including significant reduction in incidences of diabetic ketoacidosis at diagnosis, opportunities to participate in clinical trials, access to therapies that can delay onset of T1D, and time to prepare for a diagnosis. The ADA Scientific Sessions was an ideal place to present this guidance to the broader T1D scientific and professional communities." Other highlights from the sessions include: Vertex Pharmaceuticals gave a highly anticipated update on the phase I/II clinical trial of VX-880, their stem cell-derived islet cell therapy. Today, all participants who have had the therapy for at least five months have an HbA1c below 7.0% and are above target time-in-range, 11 of 12 participants have reduced or eliminated the need for external insulin, and all three individuals who received the therapy at least 12 months ago have eliminated hypoglycemic events and are fully off external insulin—meeting the primary and secondary endpoints. This research was made possible by years of funding by Breakthrough T1D and the T1D Fund to Doug Melton, Ph.D., and Semma Therapeutics—a biotech company founded by Melton to develop a stem cell-derived islet therapy for T1D—which was acquired by Vertex Pharmaceuticals. Kevan Herold, M.D., presented a secondary analysis of the phase III PROTECT clinical trial . In October 2023, Tzield™ (teplizumab-mzwv) showed that it can slow the loss of beta cells and preserve beta cell function in newly diagnosed (stage 3 T1D) children and adolescents ages eight to 17. This analysis demonstrated that, in addition to slowing down the loss of beta cells in new-onset T1D, Tzield can decrease insulin dose and improve time-in-range. This reinforces our commitment to supporting therapies that preserve beta cells at onset, which is important for the prevention of complications and improvement in new-onset clinical factors. Dr. Herold has been supported by Breakthrough T1D since the late 1980s. In his research, he showed that he could prevent autoimmune diabetes with an immune-modifying antibody (which later, became a humanized version, teplizumap) and was the lead on the clinical trial that demonstrated that teplizumab could delay the onset of T1D in people almost certain to develop the disease. In November 2022, teplizumab was approved by the FDA to delay the onset of the disease in at-risk individuals eight and older. In a Breakthrough T1D-funded study, Peter Calhoun, Ph.D., gave a fascinating talk on how continuous glucose monitors (CGMs) can predict who will move onto Stage 3 T1D earlier. He took a dataset from five screening programs—TrialNet, ASK (Autoimmunity Screening for Kids), DAISY (Diabetes Autoimmunity Study in the Young), DIPP (Type 1 Diabetes Prediction and Prevention), and BDR (Belgium Diabetes Registry)—and was able to show that incorporating CGM metrics into individual characteristics had the best predictive performance to classify individuals of the impending clinical onset of T1D. More information about Breakthrough T1D-funded research and presentations can be found on Breakthrough T1D's website. About Breakthrough T1D, Formerly JDRF As the leading global type 1 diabetes research and advocacy organization, Breakthrough T1D helps make everyday life with type 1 diabetes better while driving toward cures. We do this by investing in the most promising research, advocating for progress by working with government to address issues that impact the T1D community, and helping educate and empower individuals facing this condition. About Type 1 Diabetes (T1D) T1D is an autoimmune condition that causes the pancreas to make very little insulin or none at all. This leads to dependence on insulin therapy and the risk of short and long-term complications, which can include highs and lows in blood sugar; damage to the kidneys, eyes, nerves, and heart; and even death. Globally, it impacts nearly 9 million people. Many believe T1D is only diagnosed in childhood and adolescence, but diagnosis in adulthood is common and accounts for nearly 50% of all T1D diagnoses. The onset of T1D has nothing to do with diet or lifestyle. While its causes are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved. There is currently no cure for T1D. Contact: Casey Fielder 509-651-0087 [email protected] SOURCE JDRF International