Orca Bio Presents Positive Data Demonstrating the Potential for Orca-T and Orca-Q to Expand Treatment to Additional Patient Groups at the 65th ASH Annual Meeting

Orca Bio, a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders, today announced positive new data that suggest its investigational high-precision cell therapies, Orca-T and Orca-Q, have the potential to deliver improved clinical outcomes across different age ranges, donor types and conditioning regimens relative to existing standard of care allogeneic hematopoietic stem cell transplants (alloHSCT). The results presented at the 65th American Society of Hematology (ASH) Annual Meeting showed promising data with the use of Orca Bio's cell therapies across several patient groups where there is significant unmet medical need.

Orca-T in Older Patients with Myeloablative Conditioning

Results highlighted in an oral presentation showed Orca-T's ability to deliver similar outcomes in older patients undergoing myeloablative conditioning (MAC) as younger patients. Notably, Orca-T delivered similar results across disease control, non-relapse mortality (NRM) and overall survival (OS).

"While the use of MAC offers the best chance of a cure, it also increases life-threatening complications in older patients receiving standard of care alloHSCT," said presenting author Caspian Oliai, M.D., medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center. "These findings suggest a cell therapy like Orca-T, which has the potential to offer a cure while reducing toxicity and lowering treatment-related mortality, may allow older patients to better tolerate MAC. This approach could expand curative treatment to older patients who might not be offered a MAC regimen today, and potentially provide physicians with an important new option in our ongoing efforts to balance the risk of relapse with transplant-related side effects."

In a subgroup analysis, 64 patients from Orca Bio's ongoing multi-center Phase 1b clinical trial who received Orca-T and busulfan, fludarabine and thiotepa (BFT) conditioning for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype leukemia, chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) were divided into two age groups: 18-54 years of age (n=39), and 55 years of age and older (n=25). With a median follow-up of 12 months, the following outcomes were reported:

• Relapse-free survival (RFS) was 84.8% in younger patients and 82.3% in older patients.
• NRM was 0% in both groups.
• OS was 100% and 95.5% in the younger and older patient groups, respectively.
• Events of grade 3-4 acute graft versus host disease (GvHD) and moderate-to-severe chronic GvHD were low across the younger group (0 and 3, respectively) and older group (1 and 3, respectively).

Across all patients, Orca-T continued to be manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.

Orca-T in Older Patients with Reduced Intensity Conditioning

Additional data from a single-center open-label Phase 1 clinical trial presented at ASH looked at the outcomes of older patients treated with Orca-T and a reduced intensity conditioning (RIC). These patients were found to be unfit for a MAC regimen due to the significant risks associated with it, particularly in older age. At 12 months, patients treated with a RIC Orca-T (n=15) saw no observable compromise in curative outcomes, with no patients experiencing relapse (0%). Patients also saw encouraging RFS (79%) and a low incidence of both grade 3-4 acute and chronic GvHD (0% and 7%, respectively).

Collectively, these findings support the potential for Orca-T to treat older patients with hematological malignancies, whether they are given a MAC or RIC regimen, with no new safety signals reported.

Orca-T in Patients with MDS

New data was also presented on the performance of Orca-T in patients with intermediate to high-risk MDS. Current treatments for MDS aren't often curative, and many patients relapse or become resistant to first-line treatment. There remains an unmet need for new, more effective but tolerable strategies to manage MDS.

In this subgroup from the ongoing multi-center Phase 1b clinical trial, Orca-T demonstrated promising results in this patient population (n=16). At one year, RFS with Orca-T was 94%. No patients experienced grade 3-4 acute GvHD, and moderate-to-severe chronic GvHD occurred in two patients. The rates of NRM and OS with Orca-T were 0% and 94%, respectively.

Orca-T is currently being evaluated in a pivotal Phase 3 clinical study for the treatment of AML, ALL and MDS at leading transplant centers across the U.S.

Orca-Q for Patients with Haploidentical Donors

In an oral presentation, Orca Bio shared updated data from a multi-center Phase 1 clinical trial of its second high-precision cell therapy, Orca-Q, in patients with a haploidentical donor without the use of post-transplant cyclophosphamide (PTCy).

"Orca-Q is a first-in-class therapy that has the potential to improve patient outcomes and reduce the risk of graft versus host disease without the use of PTCy," said presenting author Samer Srour, M.D., M.S., Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. "While PTCy has increased the use of haploidentical HSCTs, it can bring a myriad of risks and toxicities that we didn't experience with Orca-Q. These updated results in an expanded group of patients continue to support Orca-Q's promise to overcome the challenges of haploidentical stem cell transplant by providing a solution where patients and physicians may no longer have to compromise between the risk of relapse and the risk of GvHD."

The positive outcomes from an expanded group of 33 patients with AML, ALL and CML support Orca-Q as a potential treatment option for patients with a haploidentical donor. With a median of 375 days follow-up, updated safety and efficacy data include:

• No patients experienced moderate-to-severe chronic GvHD (0%).
• There was one event of grade 3 acute GvHD and no grade 4 acute GvHD.
• NRM was 9%.
• RFS, GRFS and OS at one year were 82%.

Additionally, no new safety signals were identified. The estimated incidence of CTCAE grade 2 and greater than grade 3 infections at one year were 9% and 15%, respectively.

"At Orca Bio, we understand the challenges providers face in achieving the right balance in offering blood cancer patients the best option for a cure with optimal quality of life," said Ivan Dimov, Ph.D., co-founder and chief executive officer of Orca Bio. "We are pleased to present these latest findings at ASH that add to our growing body of clinical evidence which underscore the potential of our novel high-precision platform to expand potentially life-saving treatment to more patient groups who could benefit."

The full ASH presentations will be made available on www.orcabio.com.

About Orca-T

Orca-T is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies. Orca-T includes infusions containing regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T is currently being evaluated in a pivotal Phase 3 clinical trial at leading transplant centers across the U.S. and has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration.

About Orca-Q

Orca-Q is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of hematologic malignancies in patients with haploidentical donors. Orca-Q is a proprietary composition of stem cells combined with specific T-cell subsets derived from healthy donors and engineered by Orca Bio's high-precision platform. Orca-Q has the potential to improve patient outcomes and reduce the risks of toxicities without the use of post-transplant cyclophosphamide (PTCy) in patients unable to identify a full human leukocyte antigen (HLA) match.

About Orca Bio

Orca Bio is a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders. Our investigational products are designed to safely replace a patient's diseased blood and immune system with a healthy one, delivering significantly better outcomes with dramatically fewer risks than the standard of care. Our manufacturing platform uses single-cell precision to create proprietary, uniquely-defined products that have the potential to transform allogeneic cell therapy. At Orca Bio, our mission is to make curative cell therapies both more effective and safer, and in doing so, push past the field's current boundaries and redefine its future. For more information, visit www.orcabio.com and follow Orca Bio on Twitter: @OrcaBio.