On December 15, 2025 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported the publication of the Precision-T Phase 3 study results of its lead investigational allogeneic T-cell immunotherapy, Orca-T, in Blood, a journal of the American Society of Hematology (ASH) (Free ASH Whitepaper). The study compared Orca-T to a conventional allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). These results were first presented on April 2, 2025, at the 51st Annual Meeting of The EBMT in Florence, Italy, and further analyses were presented at the 67th ASH (Free ASH Whitepaper) Annual Meeting on December 6, 2025.

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In the randomized Precision-T study, Orca-T plus single-agent tacrolimus (TAC) demonstrated a significant improvement in the primary endpoint of survival free from moderate-to-severe chronic graft versus host disease (cGFS) compared to alloHSCT plus tacrolimus/methotrexate (TAC/MTX). The rate for patients who received Orca-T was 78% (95% CI: 65%, 87%) compared to 38.4% (95% CI: 26%, 51%) for patients who received an alloHSCT (HR 0.26; p<0.00001), an improvement driven by a reduction in moderate-to-severe chronic graft versus host disease (cGvHD) and fewer patient deaths.

"Today, treating patients with serious blood cancers using conventional allogeneic stem cell transplants often forces a difficult risk–benefit trade-off, as clinicians work to cure the disease while avoiding life-threatening complications like GvHD," said lead author Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Medicine. "The Precision-T results showed that Orca-T can meaningfully shift that balance, delivering improved GvHD-free survival alongside less toxicity, including fewer serious infections and lower non-relapse mortality. Orca-T has the potential to become an important new therapy for patients and a valuable new option for the providers who care for them."

In the study, all patients (n=187) with a median age of 43.6 years (range 19-65 years) were randomized 1:1 to Orca-T plus TAC or alloHSCT plus TAC/MTX. Patients across both groups received myeloablative conditioning 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. Additional results from the Precision-T study at one year include:

A secondary endpoint of cumulative incidence of moderate-to-severe cGvHD was 12.6% (95% CI: 5%, 23%) and 44.0% (95% CI: 31%, 56%) in the Orca-T and alloHSCT arms, respectively (HR 0.19; p<0.00002).
The overall survival (OS), another secondary endpoint, was 93.7% (95% CI: 86%, 97%) in the Orca-T arm and 83.2% (95% CI: 73%, 90%) in the alloHSCT arm (HR 0.49; p=0.11823).
A secondary endpoint of GvHD and relapse-free survival (GRFS) was 63.1% and 30.9% with Orca-T and alloHSCT (p<0.001 in a post hoc analysis), respectively.
The cumulative incidence of non-relapse mortality (NRM) was 3.4% (95% CI: 0.9%, 8.8%) for Orca-T versus 13.2% (95% CI: 6.8%, 21.6%) for alloHSCT (HR 0.27 [95% CI: 0.08, 0.93]; p=0.03 in a post hoc analysis).

Additional safety findings were consistent with previous studies. The cumulative incidence for grade III or IV acute GvHD at day +180 was reduced with Orca-T with 6.2% (95% CI: 2.3, 12.9) versus 16.5% (95% CI: 9.4, 25.3) with alloHSCT (HR 0.37 [95% CI: 0.13, 1.02]; p=0.044 in a post hoc analysis). Grade 3+ infections were less common with Orca-T, with a one-year estimated incidence of 8.4% (95% CI: 3.6%, 16%) for Orca-T and 16.1% (95% CI: 9.2%, 25%) for alloHSCT.

An exploratory endpoint evaluated health-related quality of life (HRQoL) and hospitalization patterns and found Orca-T delivered marked improvements over conventional alloHSCT. In the data presented at ASH (Free ASH Whitepaper) 2025, patients receiving Orca-T experienced faster recovery to, and higher improvement above, baseline HRQoL, fewer ICU stays, lower likelihood of rehospitalization and higher rehospitalization-free survival, suggesting better early post-treatment recovery and a lower burden of GvHD symptoms.

Rehospitalizations due to adverse events occurred less frequently among Orca-T recipients (27.3% [24] vs. 45.7% [43]), with fewer total hospitalization days per patient (30.6 vs. 40.8). Rehospitalization-free survival at 18 months was also significantly improved with Orca-T, reaching 66.4% (95% CI: 54.0, 76.2) compared to 33.8% (95% CI: 18.5, 49.9) for conventional alloHSCT (p=0.0096 in a post hoc analysis; HR 0.53 [0.32, 0.86]).

"As the first Treg-based immunotherapy to show improved outcomes for patients with acute leukemias and myelodysplastic syndrome compared with a conventional transplant, Orca-T has the potential to become a new standard of care," said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio. "The Phase 3 results published in Blood underscore our ability to potentially redefine how blood cancers are treated today. We look forward to continuing to work closely with the FDA on the review of our application with the goal of making Orca-T available to patients who need it."

The safety and efficacy of Orca-T have not been determined by any regulatory authority. Orca-T is currently being evaluated under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

About Precision-T
Precision-T (NCT05316701) is a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, compared to conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Orca Bio received guidance from the U.S. Food and Drug Administration on the design of Precision-T, which evaluated Orca-T in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). There are 19 leading treatment centers participating in the trial, which enrolled 187 patients across the U.S.

About Orca-T
Orca-T is an investigational allogeneic T-cell immunotherapy under evaluation for the treatment of multiple hematologic malignancies including acute leukemias and myelodysplastic syndromes. Orca-T is composed of highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designation for the prevention of graft versus host disease or death in patients eligible for hematopoietic stem cell transplant from the U.S. Food and Drug Administration (FDA). The Biologics License Application (BLA) for Orca-T is currently under Priority Review with the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

(Press release, Orca Bio, DEC 15, 2025, https://orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies-2/?utm_source=rss&utm_medium=rss&utm_campaign=orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies-2 [SID1234661426])

(Press release, Orca Bio, DEC 15, 2025, https://orcabio.com/orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies-2/?utm_source=rss&utm_medium=rss&utm_campaign=orca-bio-announces-positive-results-from-the-pivotal-phase-3-study-of-investigational-orca-t-compared-to-allogeneic-stem-cell-transplant-for-the-treatment-of-hematologic-malignancies-2 [SID1234661426])

On December 15, 2025 Pilatus Biosciences Inc., a biopharmaceutical company developing novel metabolic checkpoint immunotherapies for liver and gastrointestinal cancers, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for PLT012, a first-in-class anti-CD36 monoclonal antibody, to enter clinical development for the treatment of solid tumors. Pilatus plans to initiate this Phase 1 clinical trial in the first quarter of 2026.

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PLT012 is a first-in-class metabolic checkpoint antibody designed to block CD36-mediated lipid uptake and immune suppression within the tumor microenvironment. CD36 is an immunometabolic regulator highly expressed on exhausted T cells, regulatory T cells, and tumor-associated macrophages, but is far less prevalent in healthy tissues.

By targeting CD36, PLT012 is engineered to restore metabolic fitness in cytotoxic T cells, reduce immunosuppressive cell populations, and promote stronger anti-tumor immune responses. In preclinical models, PLT012 demonstrated monotherapy activity across immune-hot and immune-cold tumors and showed potential synergy with PD-1/PD-L1 inhibitors, supporting its development as both a single agent and a combination therapy.

"PLT012 represents a fundamentally new approach to treating solid tumors by addressing the metabolic dysfunction that underlies immune exhaustion," said Raven Lin, Ph.D., Co-Founder and CEO, Pilatus Biosciences. "Leveraging our deep expertise in metabolic immunology, PLT012 was developed to simultaneously enhance effector T cell function and suppress tumor-promoting immune populations, while maintaining a favorable safety profile. We believe this dual-action metabolic checkpoint mechanism has the potential to deliver meaningful benefits for patients whose tumors do not respond to existing immunotherapies. We look forward to initiating our Phase 1 clinical trial of PLT012 early next year."

"Targeting CD36 represents a promising new way to reshape the tumor microenvironment," said the trial lead principal investigator, Anthony El-Khoueiry, M.D., Verna R. Richter Chair in Cancer Research, Associate Director for Clinical Research and Chief of Section of Developmental Therapeutics/Phase I Program at USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, and Associate Professor of Clinical Medicine at Keck School of Medicine of USC. "PLT012’s ability to modulate metabolic dysfunction and reinvigorate exhausted T cells positions it as a potentially important therapeutic option for tumors that do not respond to current immunotherapies."

The upcoming Phase 1, first-in-human clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary signs of clinical activity, with expansion cohorts planned for tumor types strongly influenced by CD36-mediated metabolic dysregulation. Pilatus has also received FDA Orphan Drug Status for PLT012 for the treatment of liver and intrahepatic bile duct cancers.

"The hepatic microenvironment is tolerogenic and macrophage-rich which can dampen effector T-cell activity, contributing to weaker responses to immunotherapy treatments for HCC and liver metastases," said Anthony W Tolcher, M.D., FRCPC, FACP of New Experimental Therapeutics (NEXT), San Antonio, Texas. "Preclinical data has shown that PLT012 can overcome this immunogenically cold environment and elicit strong anticancer effects, which we hope will be translated into improved patient outcomes in the planned Phase 1 clinical trial."

About PLT012

PLT012 is a humanized monoclonal antibody designed to selectively block CD36-mediated lipid uptake, a key mechanism driving immunosuppression and immune exclusion within the tumor microenvironment. By targeting lipid metabolism, PLT012 exerts a unique mechanism of action: it reduces immunosuppressive cell populations, including Tregs and pro-tumor macrophages, while simultaneously enhancing anti-tumor activities of intratumoral NK cell and cytotoxic CD8+ T cell that are otherwise susceptible to lipid-induced exhaustion. In preclinical studies, PLT012 has demonstrated potent monotherapy efficacy in models of liver malignancies, with a favorable safety profile across species. Leveraging its distinct mechanism of action, PLT012 further acts as a potent sensitizer in combination with anti–PD-L1 therapies, effectively overcoming drug resistance in immune "cold" tumors and liver metastases.

(Press release, Pilatus Biosciences, DEC 15, 2025, View Source [SID1234661446])

On December 15, 2025 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported positive in vivo results, indicating that opaganib combined with venetoclax reduces Chronic Lymphocytic Leukemia (CLL) cells by half compared to controls, and further demonstrates opaganib’s potential as an add-on therapy to venetoclax in venetoclax-resistant CLL.

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"Understanding mechanisms of resistance to targeted therapies such as the BCL-2 inhibitor venetoclax is essential to improve current treatment strategies and may provide key insights to personalize treatment for chronic lymphocytic leukemia (CLL) patients" said Romina Gamberale, PhD, Independent Researcher at CONICET from the Institute of Experimental Medicine (IMEX, CONICET-National Academy of Medicine) in Buenos Aires, Argentina, who led the study. "Our previous ex vivo work has shown that sphingosine kinase 2 (SPHK2) is overexpressed in venetoclax-resistant CLL cells and that inhibiting SPHK2 may reduce T-cell-induced resistance and resensitize previously resistant cells. The results of this in vivo study in mice indicate that adding opaganib, a potent SPHK2 inhibitor, to venetoclax reduced CLL cell counts by 50% compared to controls, showing that opaganib may have a significant role to play in mitigating BCL-2 inhibitor resistance."

Dr. Mark Levitt, Chief Scientific Officer at RedHill said: "Venetoclax is a key CLL therapy and finding ways to maintain its effectiveness, and to reduce the potential for resistance-related treatment failure, could represent a breakthrough in the ability to treat CLL patients. This promising data supports the hypothesis that opaganib, as a potent inhibitor of SPHK2, provides a potential route to maintaining venetoclax effects in treating CLL. Opaganib has shown potential as add-on therapy in several preclinical oncology models and is currently undergoing a Phase 2 clinical trial in combination with darolutamide in advanced prostate cancer. This new data now adds CLL to the list of potential cancer indications where opaganib has shown potential to bring additive therapeutic value."

Opaganib has a safety and tolerability profile shown in more than 470 clinical trials / expanded access participants. It targets multiple oncology, virology, inflammation, medical countermeasures, diabetes and obesity indications, with several U.S. government partnerships, including BARDA funding, in place.

Approved by the FDA in 2016, venetoclax (Venclexta and Venclyxto, Abbvie / Genentech), is a first-in-class BCL-2 inhibitor that has become a mainstay of CLL therapy, achieving sales of approximately $2.5 billion in 2024. Venetoclax works by blocking a protein called BCL-2, which is often overproduced in certain cancer cells and prevents the process of apoptosis (programmed cell death) – helping to keep the cancer cells alive and growing. By binding to, and inhibiting, the BCL-2 protein, venetoclax enables the cancer cells to undergo apoptosis and die.

About Chronic Lymphocytic Leukemia (CLL)

CLL is a slow-growing blood and bone marrow cancer that affects a type of white blood cell called lymphocytes. It is the most common type of leukemia in adults and has a highly variable clinical course. It is generally not considered to be curable.

About Opaganib (ABC294640)

Opaganib is a first-in-class, proprietary investigational host-directed and potentially broad-acting orally administered drug with anticancer, anti-inflammatory and antiviral activity. Opaganib is targeted at multiple potential oncology, radioprotection, viral, inflammatory, and gastrointestinal indications, including several cancers, diabetes and obesity-related disorders, gastrointestinal acute radiation syndrome (GI-ARS), COVID-19, Ebola and other viruses as part of pandemic preparedness. Opaganib has also shown positive preclinical results in renal fibrosis.

Opaganib has received orphan-drug designations from the FDA in cholangiocarcinoma and neuroblastoma. It is currently undergoing a Phase 2 clinical trial in combination with darolutamide in advanced prostate cancer and has previously undergone studies in advanced cholangiocarcinoma (Phase 2a). Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.

Opaganib is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

Several U.S. government medical countermeasures and pandemic preparedness programs have selected opaganib for evaluation for multiple indications, including GI-ARS, Ebola virus disease and others. Funding bodies include the Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. government Department of Health & Human Services’ National Institutes of Health, and the Administration for Strategic Preparedness and Response’s (ASPR) Center for Biomedical Advanced Research and Development Authority (BARDA).

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury, Gilead Sciences Inc.), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study.

Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in Microorganisms.

(Press release, RedHill Biopharma, DEC 15, 2025, View Source [SID1234661428])

On December 15, 2025 Dren Bio, a privately held, clinical-stage biotechnology company developing first-in-class myeloid cell engager therapeutics, reported that it has entered into a strategic collaboration with Sanofi (NASDAQ: SNY) for the discovery and development of a next-generation B-cell depleting therapy for the treatment of various autoimmune diseases.

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The new agreement builds on the existing relationship between the two companies, following Sanofi’s acquisition earlier this year of Dren Bio’s DR-0201 program for deep B-cell depletion. DR-0201, now known as SAR448501, is currently being evaluated in two ongoing phase 1 studies and has shown robust B-cell depletion, with the potential to induce sustained treatment-free remission in patients with autoimmune diseases.

"Our newly expanded strategic alliance with Dren Bio reflects Sanofi’s deep commitment to developing best-in-class therapies with the potential to achieve remission in patients with immune-mediated diseases," said Alyssa Johnsen, Global Therapeutic Head, Immunology and Oncology Development at Sanofi. "By combining Dren Bio’s unique scientific approach with Sanofi’s development expertise, we aim to accelerate the development of innovative therapies for patients in need."

Amit Mehta, Ph.D., Chief Operating Officer and Chief Business Officer of Dren Bio, added, "Sanofi has been a valued partner in unlocking the full potential of deep B-cell depletion through the acquisition of DR-0201, and we’re thrilled to expand our collaboration by further leveraging the capabilities of our Targeted Myeloid Engager and Phagocytosis platform. The U.S. profit/loss share option allows us to partner with a global commercial leader and represents an important milestone in our growth into a fully integrated biopharmaceutical company."

Under the terms of the agreement, Dren Bio will receive an upfront payment of $100 million and is eligible to receive up to $1.7 billion in development, regulatory, and commercial milestone payments. The companies will collaborate on discovery and preclinical development activities leveraging Dren Bio’s proprietary platform. Following development candidate selection, Sanofi will assume subsequent responsibility for development, manufacturing, regulatory, and commercialization efforts. Dren Bio has the option to enter into a U.S. profit/loss sharing arrangement with Sanofi. If exercised, Dren Bio will co-fund 40% of ongoing global development costs in exchange for U.S. co-promotion rights and a 50/50 share of U.S. profits and losses. Dren Bio will also remain eligible to receive milestones and tiered royalties on net sales outside the United States.

(Press release, Dren Bio, DEC 15, 2025, View Source [SID1234661447])

On December 15, 2025 Strand Therapeutics, a leader in next-generation mRNA-based therapeutics, reported that Jake Becraft, PhD, Co-founder and Chief Executive Officer, will present at the 44th Annual J.P. Morgan Healthcare Conference on Wednesday, January 14, 2026, at 10:30 AM PT.

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"2025 was a transformative year as we moved programmable mRNA from promise to proof, delivering clinical results that have the potential to redefine what’s possible in oncology," said Dr. Becraft. "Strand is programming conditional therapeutic protein expression into the mRNA itself, enabling it to sense its environment and activate selectively within the target. We’re entering 2026 with clinical momentum and a platform that positions us at the forefront of the next generation of genetic medicine."

In 2025, Strand achieved multiple expansive milestones and validation with significant progress across clinical development, pipeline expansion, and corporate growth:

Clinical validation: Presented first-in-human Phase 1 data for STX-001 at the ASCO (Free ASCO Whitepaper) Annual Meeting, demonstrating response rates in late-stage cancer patients who had exhausted other treatment options
Capital to scale: Closed a $153 million Series B financing led by Kinnevik with participation from Regeneron Ventures, ICONIQ, Amgen Ventures, Eli Lilly, and other leading pharma investors
Pipeline acceleration: Unveiled preclinical data for STX-003 at the AACR (Free AACR Whitepaper) Annual Meeting, advanced ongoing solid tumor trials, progressed multiple programs to support 2026 clinical entry for STX-003, and expanded into in vivo CAR-T therapy
Board and leadership expansion: Appointed Jeb Keiper to Strand’s Board of Directors; Jason J. Luke, MD, FACP, as Chief Medical Officer; Prashant Nambiar, DVM, PhD, MBA, as Chief Scientific Officer; and Ethan Cash as Senior Vice President of Portfolio Management and Program Development

(Press release, Strand Therapeutics, DEC 15, 2025, View Source [SID1234661448])