Tacrolimus

Orca Bio\'s Orca-T was tied to a 78% rate of survival free of moderate to severe chronic graft-versus-host disease at one year, a statistically significant improvement over the 38% rate seen in patients receiving allogeneic stem cell transplants.\n In a late-stage trial of patients with multiple types of blood cancer, Orca Bio’s allogeneic T-cell immunotherapy doubled the rate at which patients survived without developing chronic graft-versus-host disease (cGVHD) at one year compared with conventional allogeneic stem cell transplants (alloHSCT).“This was the dream that we\'ve had from the beginning of the company—really being able to help these patients who have no options,” Orca Bio CEO and cofounder Ivan Dimov, Ph.D., told Fierce Biotech.“It\'s a very difficult trade-off balance that physicians are always playing, because on the one hand, you want to cure that cancer—which, if you don\'t—can end up killing the patient,” he said. “But at the same time, you\'re very afraid of giving them secondary toxicities that, again, can either kill you or can cause a lifelong problem.”Dimov believes the late-stage trial demonstrates for the first time that people don’t have to “play that trade-off game.” Orca\'s cell therapy provides “good efficacy and low toxicity,” the CEO explained, deeming this combination of features as the “the holy grail” in the space.The California-based biotech is already in talks with the FDA and plans on submitting a biologics licensing application (BLA) sometime this year. Orca Bio’s open-label phase 3 study enrolled 187 patients with acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome and mixed-phenotype acute leukemia, according to a March 17 release.Patients were randomized to receive either Orca’s cell therapy, known as Orca-T, or standard of care. Participants in the investigational arm also received single-agent tacrolimus, while the comparator cohort received alloHSCT plus tacrolimus methotrexate—a standard GVHD prophylaxis that is tied to several toxicities. All patients received myeloablative conditioning.The trial’s primary endpoint measured survival free of cGVHD, a possible transplant complication in which the donor\'s immune cells attack the patient’s tissues and organs. “cGVHD is one of those huge drivers of toxicity which, in many cases, can be deadly, but in in other cases, it\'s a lifelong disease,” Dimov explained. “So, you end up trading your cancer for this other lifelong, horrible disease, if you\'re lucky to survive.”Orca-T was tied to a 78% rate of survival free of moderate to severe cGVHD at the trial\'s one-year mark, a statistically significant improvement over the 38% rate seen in patients who received alloHSCT. Participants in the Orca-T arm had a median follow-up time of 11 months, while patients in the alloHSCT arm had a median follow-up of 11.5 months.The rate of overall survival—a secondary endpoint—was 94% for Orca-T patients at one year versus 83% for standard of care.The rate of relapse-free survival was 76% and 74% in the Orca-T and alloHSCT arms, respectively.“What this result shows you is that we can significantly drop that bad outcome and really give life to people, and that\'s led to an incredible overall survival rate of 94%, which is unprecedented in the literature and all previous trials,” Dimov said. “It\'s really incredible to see and it hasn\'t come at the expense of higher relapse rates.” Moderate to severe cGvHD occurred in 13% of patients receiving the investigational cell therapy, compared to 44% of patients with alloHSCT.The cumulative incidence of non-relapse deaths was 3% in the Orca-T arm and 13% in the alloHSCT group.On the safety side, grade 4 or 5 infections occurred in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively. No new safety issues were identified, according to the biotech.Complete results from the trial, dubbed Precision-T, will be presented April 2 at the 51st Annual Meeting of the EBMT in Italy. “We\'re right now engaging the FDA in pretty deep discussions,” Dimov said, adding that the biotech has shared the phase 3 data with the agency and will have more clarity on a specific timeline for a BLA submission after the conversations wrap up.“Our goal is to do it as quickly as possible and bring this to patients,” the CEO said.The biotech is already ramping up for possible commercialization, expanding across manufacturing, regulatory, medical and commercial teams, according to Dimov. As of now, Orca Bio employs 150 to 200 people, the CEO said. When asked about the obstacles other cell therapy makers have faced—such as manufacturing and accessibility issues—Dimov said Orca Bio has “the advantage of not being the very first cell therapy.”“We\'ve been able to see some of these issues and prepare for them ahead of time,” he said, noting that while Orca-T wouldn’t be the first cell therapy marketed, it could become the first allogeneic T-cell immunotherapy to gain U.S. approval.“We\'ve been able to streamline our manufacturing process and really get it down to about 24 to 48 hours,” Dimov said. “All of our patients have a vein-to-vein time of less than 72 hours.”That means that donor cells are collected and transported to a manufacturing facility, where the product is produced and then sent to the hospital for patient infusion—all within 72 hours.“That kind of turnaround time is almost unheard of in the cell and gene therapy space,” according to Dimov.The company has also invested “heavily” into a 100,000-square-foot commercial manufacturing facility that is expected to generate about 3,000 doses a year at its peak, a number Dimov said would represent about 30% of all transplants occurring in the U.S.  Orca Bio is powered by a $192 series D raised in 2020, with a total of $300 million secured since being founded in 2016. When asked what the biotech’s next steps would be for procuring further financing, Dimov said the company is open to various options.“We\'ve been very fortunate to be able to remain private and focus on delivering for patients,” he told Fierce. “We have the ability to get this product through the approval process and launch it in the U.S.”That being said, Orca Bio is “always opportunistic about expansion opportunities,” Dimov said.“Our North Star here is get this to be as broadly impactful to patients as possible—across diseases, geographies, volumes, etc.,” the CEO said. “Whether it\'s raising more private money, whether it\'s going public, whether it\'s partnering with a large pharma, if some of these potential pathways will help us significantly in that fundamental goal, of course, we will consider it very seriously.”Ultimately, Dimov views Orca-T as a “potentially standardizing curative treatment,” explaining that standard allogeneic stem cell transplants are one of the few treatments for advanced cancer patients delivered with fully curative intent.However, there’s no standardized regimen for the treatment, with hospitals across the country conducting different kinds of supportive regimens. If Orca-T becomes the first allogeneic T-cell immunotherapy to gain FDA approval, Dimov believes it would help standardize the way patients are treated across different sites.    The phase 3 results are also a “strong confirmation” of Orca Bio’s precision platform, according to Dimov, which helped produce another clinical-stage allogeneic T-cell immunotherapy dubbed Orca-Q. The asset is being studied in leukemia and is queued up for testing in autoimmune diseases. 

MENLO PARK, CA, March 17, 2025 – Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, today announced positive results from the pivotal Phase 3 Precision-T study of Orca-T, its lead investigational allogeneic T-cell immunotherapy, in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). Orca-T is manufactured using highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. In the randomized Precision-T study, Orca-T met the primary endpoint of a statistically significant improvement in survival free of moderate-to-severe chronic graft versus host disease (cGvHD) with Orca-T. At one year, the rate for patients who received Orca-T was 78% compared to 38% for patients who received a conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Patients in the Orca-T group achieved an estimated overall survival (OS) of 94% compared to 83% in the alloHSCT arm at one year. "Today, treating patients with serious blood cancers using allogeneic stem cell transplants requires a difficult risk-benefit trade-off as clinicians aim to cure the disease while avoiding potentially deadly treatment-related toxicities, like GvHD," said presenting author Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care. "The Precision-T study showed double the rate of survival free from GvHD with Orca-T versus a conventional transplant, a relapse-free survival rate of 76% and no new safety concerns. These findings are highly encouraging and provide compelling new evidence as we work to solve for the critical factors contributing to the needs of this patient population." Precision-T Study Results In the study, all patients (n=187) with a median age of 43.5 years (range 19-65 years) were randomized 1:1 to Orca-T plus single-agent tacrolimus (TAC) or alloHSCT plus TAC methotrexate (TAC/MTX). Patients across both groups received myeloablative conditioning (MAC) and used a related or unrelated matched donor. Patients had a median follow-up time of 11.4 months (range 0.2-24.3 months) across both arms. Key results from the Precision-T study at one year are summarized below: The primary endpoint of survival free of cGvHD was 78% (95% CI: 65%, 87%) in the Orca-T arm (n=93) and 38% (95% CI: 26%, 51%) in the alloHSCT arm (n=94) (HR 0.26; p<0.00001). An interim analysis of the secondary endpoint of OS was 94% (95% CI: 86%, 97%) in the Orca-T arm and 83% (95% CI: 73%, 90%) in the alloHSCT arm (HR 0.49; p=0.11823). An additional secondary endpoint of cumulative incidence of moderate-to-severe cGvHD was 13% (95% CI: 5%, 23%) and 44% (95% CI: 31%, 56%) in the Orca-T and alloHSCT arms, respectively (HR 0.19; p<0.00002). Exploratory endpoints at one year include the rate of relapse-free survival which was 76% and 74% in the Orca-T and alloHSCT arms, respectively (HR 0.80, p=0.49). The cumulative incidence of non-relapse mortality was 3% in the Orca-T arm and 13% in the alloHSCT arm. Additionally, the cumulative incidence of Grade 3 or 4 acute GvHD was 6% and 17% in the Orca-T and alloHSCT arms, respectively. No new safety issues were identified with Orca-T. Grade ≥ 4 infections per CTCAE scoring were noted in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively. Orca-T was manufactured in Orca Bio’s centralized GMP facility and delivered to patients at 19 treatment centers across the U.S., with all infusions occurring within a vein-to-vein time of 72 hours or less. “Approximately 46,000 people are diagnosed with AML, ALL and MDS in the U.S. each year, but only a fraction of them receive an allogeneic stem cell transplant within the current paradigm,” said Rawan Faramand, M.D., Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center. “Additional treatment options are needed, and the introduction of a cell therapy like Orca-T that leverages a precision-based approach could pave the way for a new standard of care for patients with various hematologic malignancies.” “These exciting results underscore Orca Bio’s vision of transforming the treatment landscape for patients living with serious blood cancers, potentially standardizing curative treatment for diseases like AML, ALL and MDS,” said Ivan Dimov, Ph.D., co-founder and chief executive officer at Orca Bio. “We are working closely with the FDA and expect to submit a Biologics License Application this year. These results support the validity of our high-precision platform as we continue to advance our robust pipeline of allogeneic cell therapies for the treatment of hematologic malignancies, autoimmune diseases and beyond.” Orca Bio is grateful to the patients and families, donors and trial site investigators who participated in the Precision-T study. The complete results will be presented on April 2, 2025, at the 51st Annual Meeting of The EBMT in Florence, Italy.