On December 12, 2022 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, reported additional positive clinical data from its Phase 1 clinical trial of NX-2127 in two oral sessions by Anthony Mato, M.D., MSCE, former director of the Chronic Lymphocytic (CLL) Program at Memorial Sloan Kettering Cancer Center, and Omar Abdel-Wahab, M.D., Chair of Sloan Kettering Institute (SKI) Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center (Press release, Nurix Therapeutics, DEC 12, 2022, View Source [SID1234625219]). NX-2127 is a once daily, oral, investigational new drug that combines BTK degradation with immunomodulatory activity. The podium presentations took place at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition which is being held in New Orleans, Louisiana.

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"These early Phase 1 data demonstrate that NX-2127 effectively degrades BTK resulting in clinically meaningful responses independent of prior treatments or BTK mutational status and offering a potential new treatment modality for patients who have otherwise exhausted other approved and emerging treatment options," said Robert J. Brown, M.D., Nurix’s executive vice president of clinical development.

The data presented by Dr. Mato demonstrate that treatment with NX-2127 results in sustained BTK degradation and clinically meaningful responses in heavily pretreated patients with relapsed/refractory CLL independent of prior treatments or BTK mutational status. These presentations included preliminary data from 36 adults with relapsed/refractory B-cell malignancies enrolled in the Phase 1a/b study, including 23 patients with CLL who had undergone and failed a median of five prior therapies including a BTK inhibitor. Approximately 78% of this group had previously received both BTK and BCL2 inhibitors and 35% had been treated with the non-covalent BTK inhibitor pirtobrutinib. Of the CLL patients, 48% had one or more identified BTK resistance mutations prior to treatment with NX-2127. Following treatment with NX-2127 in this heavily pretreated CLL population, sustained BTK degradation and decreased B cell activation were observed regardless of prior treatment and baseline BTK mutation status with an overall response rate (ORR) of 33% (95% CI 12–62%). As of September 21, 2022, the data cut-off date, the median follow up was 5.6 months (0.3 to 15.7 months), and 14 of 23 patients remained on treatment. Importantly, the safety profile of NX-2127 was consistent with prior results from the Phase 1a portion of the trial and reports for BTK-targeted therapies in heavily pretreated patients with B cell malignancies.

"We are excited by the growing body of data generated in our Phase 1a/1b clinical trial of NX-2127 which highlights the significant differentiation and potential advantages of BTK degradation over BTK inhibition, especially in the setting of resistance to existing therapies," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We continue to explore the promise of this first-in-class targeted protein degrader of BTK as we enroll additional CLL patients in the ongoing expansion cohort and continue to enroll patients with non-Hodgkin lymphoma in the dose escalation. We look forward to additional clinical updates in 2023."

The presentation by Dr. Abdel-Wahab highlighted critical scientific findings underlying the emergence of new BTK inhibitor resistance mutations that lack BTK’s enzymatic function but still drive tumor growth. These so-call "kinase deficient" and "kinase dead" mutations underscore the importance of BTK’s scaffolding function, which is uniquely addressable by the BTK degrader modality. In the presentation, five different clinically emergent BTK resistance mutations were analyzed and categorized as kinase proficient, kinase deficient, or kinase dead, each conferring a different spectrum of resistance to available therapies. NX-2127 was found to be broadly active against all these mutations. These findings translated into clinically meaningful BTK degradation in the Phase clinical 1 trial and clinical activity independent of baseline BTK mutations.

Webcast details

The live KOL webcast event, which will begin at 8:30 pm CT (9:30 pm ET) on Monday, December 12, 2022, and the subsequent replay, will be available in the Investors section of the Nurix website under Events and Presentations.

About the Phase 1, Study of NX-2127

The multicenter Phase 1 study is designed to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary clinical activity of orally administered NX-2127 in adult patients with relapsed or refractory B-cell malignancies. The study is being conducted in two parts. The Phase 1a element is a dose-escalation study in which cohorts of patients will receive ascending oral doses of NX-2127 once daily to determine the maximum tolerated dose (MTD) and/or the optimal Phase 1b dose based on safety and tolerability. The second portion of the study, Phase 1b, is a dose expansion phase in which cohorts of patients with specific cancers will receive NX-2127 to further evaluate the safety and clinical activity of the recommended dose. The study is expected to enroll eligible patients with the following cancers: chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Waldenstrom macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL), who have required and received prior systemic therapies. Additional information on the clinical trial can be accessed at ClinicalTrials.gov (NCT04830137).

About NX-2127

NX-2127 is a novel bifunctional molecule that degrades Bruton’s tyrosine kinase (BTK) and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies.

On December 12, 2022 Agilent Technologies Inc. (NYSE: A) reported that the U.S. Food and Drug Administration (FDA) has approved Agilent Resolution ctDx FIRST as a companion diagnostic (CDx) to identify advanced non-small cell lung cancer (NSCLC) patients with KRAS G12C mutations who may benefit from treatment with KRAZATITM (adagrasib) (Press release, Agilent Technologies, DEC 12, 2022, View Source [SID1234625190]).

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This is the first liquid biopsy NGS assay approved by the FDA as a CDx for the newly approved KRAZATI in advanced NSCLC and was developed in collaboration with Mirati Therapeutics. ctDx FIRST has also been approved by the FDA for tumor profiling of the epidermal growth factor receptor (EGFR) gene for use by qualified health care professionals in accordance with professional guidelines in oncology patients with NSCLC.

As a professional service*, the ctDX FIRST test report includes broad genomic profiling on 109 genes across four types of alterations: single nucleotide variants (SNVs), insertions and deletions (indels), copy number amplifications (CNAs), and fusions.

Lung cancer is one of the most prevalent cancers among men and women in the U.S. and is the leading cause of cancer mortality, comprising 25% of all cancer-related deaths.1 Most patients with NSCLC are diagnosed at later disease stages due to undetected early symptoms.2 Approximately 14% of NSCLC patients harbor a KRAS G12C mutation, and approximately 32% of NSCLC patients have a mutation within their EGFR gene, making this new test an attractive solution to inform treatment decisions for these patients. 3,4 ctDx FIRST provides NSCLC patients and their oncologists with a new minimally invasive blood test to help clarify precision treatment options.

The ctDx FIRST assay uses novel propriety technology to detect genomic alterations in circulating tumor DNA (ctDNA) from plasma. This minimally invasive approach is preferred by 90% of cancer patients compared to more invasive tissue biopsy tests.5 In addition, liquid biopsy overcomes some limitations encountered with tissue-based methods providing a notably faster turn-around time to potentially accelerate treatment decisions.6

"Expanding access to accurate and fast genomic profiling is an essential step to unlocking important medicines for patients in desperate need," said Kenna Anderes, Mirati’s Vice President of Translational Medicine and Companion Diagnostics. "We appreciate the opportunity to partner with companies like Agilent who are committed to creating more opportunities for ‘decision medicine’ for people living with cancer."

"We are thrilled to partner with Agilent as they work to create greater access to efficient, effective and minimally-invasive tests to support clinicians with information that is critical to their patient care," said Alan Sandler, M.D., Mirati’s Chief Medical Officer. "At Mirati, we are focused on creating meaningful impacts on the lives of people with cancer. Tests like ctDx FIRST are important to realizing our commitment to patients."

"Commercializing the ctDx FIRST test enables us to support clinicians to positively impact the lives of patients with advanced NSCLC," said Sam Raha, Agilent’s President of the Diagnostics and Genomics Group. "Agilent values opportunities to partner with Mirati and other pharmaceutical companies in developing clinically relevant NGS-based diagnostics that enhance confidence in targeted cancer therapy."

To learn more about the test and order visit http://www.agilent.com/genomics/ctDxFIRST

* CLIA validated, not FDA approved

On December 12, 2022 AvenCell Therapeutics, Inc. reported updated safety and efficacy data from its lead CD-123-directed Universal CAR T Cell Candidate ("UniCAR") (Press release, AvenCell Therapeutics, DEC 12, 2022, View Source [SID1234625187]). These data, based on AvenCell’s Universal Targeting platform, were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, Louisiana.

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The oral presentation (#979) included updated data from the first-in-human phase I dose escalation study of AVC-101 in patients with relapsed/refractory acute myeloid leukemia (r/r AML) designed to assess safety and tolerability and identify an MTD. Secondary and exploratory objectives include efficacy, biological activity, and PK.

As of October 13, 2022, of 16 patients treated with AVC-101, five patients (31%) achieved complete response with incomplete count recovery (CRi) or MRD negative conversion and the overall response rate was 56% (n=9). Of evaluable patients with minimal residual disease (MRD+; n=2), both converted to MRD negative status after the treatment.

"The AVC-101 [UniCAR CD123] program shows extremely promising results in the most challenging AML patients who have exhausted all options," said Prof. Dr. med. Martin Wermke, head of Early Clinical Trial Unit at University Hospital Carl Gustav Carus in Dresden, Germany. "This study shows preliminary evidence of clinical efficacy including multiple CRs in the dose escalation stage, manageable toxicity, and proof of principle that the switchable technology can be turned on and off to manage toxicities thereby enabling targets too challenging for traditional CAR Ts. We are hopeful for additional trials of this platform to build on this encouraging data."

The presentation reports results from 16 heavily pre-treated R/R AML patients with a median of six prior lines of therapies (min-max: 2-9 lines), with nine patients having received a prior allogeneic hematopoietic stem cell transplantation. Median age of patients was 64.5 (range 18-80), with four patients over the age of 70.

"We are excited to be at ASH (Free ASH Whitepaper) for the first time as AvenCell and to showcase the Universal Targeting platform, which has the potential to address some of the most difficult efficacy and safety challenges with cell therapies seen to date," said Andrew Schiermeier, Ph.D., chief executive officer, AvenCell Therapeutics. "The data presented by Dr. Gerhard Ehninger is indicative of the promise of the platform to treat a multitude of difficult cancer targets, where the ability to precisely and reliably control CAR T cell activity in vivo after administration is critical."

About AVC-101

AVC-101 is an investigational CD-123-directed cell therapy targeting acute myeloid leukemia, that utilizes AvenCell’s proprietary Universal Targeting platform, a regulatable CAR T cell technology that can turn CAR T cells "OFF" and "ON" by means of a separately infused Targeting Module. With AVC-101, AvenCell is aiming to create a solution to address the heterogeneity and aggressive nature of acute myeloid leukemia. CD123 is a target in acute myeloid leukemia, but its on-target off-tumor toxicity makes a conventional CD-123-directed CAR very challenging.

AvenCell’s proprietary Universal Targeting Platform is part of a new paradigm in cell therapy through one-time engraftment of Universal CAR T Cells, which can then be controlled in vivo with the separate administration of Targeting Modules that direct the Universal CAR T cells to cancer cells for activation and killing. The platform’s ability to control CAR T activity after infusion via repeatable, titratable, and switchable Targeting Module infusion provides extensive flexibility to address such issues as avoiding T cell exhaustion, antigen escape, and reacting rapidly to any potential adverse events.

AVC-101 is not approved for any indication in any geography and has not been demonstrated safe or effective for any use.

On December 12, 2022 reported that updated clinical data for its CD20xCD3 T-cell engaging bispecific antibodies, including five oral presentations, were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, December 10-13, 2022 (Press release, Genentech, DEC 12, 2022, View Source [SID1234625185]). Updated results for the investigational bispecific glofitamab in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) suggest glofitamab has the potential to be the first off-the-shelf CD20xCD3 T-cell engaging bispecific antibody that can be given for a fixed period of time to people with heavily pretreated aggressive lymphoma. These data will be presented at the meeting and simultaneously published online in the New England Journal of Medicine (NEJM). Additionally, updated data for mosunetuzumab continued to demonstrate clinically meaningful outcomes in people with heavily pretreated follicular lymphoma (FL). Mosunetuzumab is a fixed-duration treatment that can be administered in the outpatient setting, which could allow people the possibility of experiencing a lasting remission with a treatment-free period.

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"We pioneered the development of T-cell engaging bispecific antibodies for lymphoma with the aim of expanding treatment options for people with difficult-to-treat blood cancers," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "New glofitamab and mosunetuzumab data continue to demonstrate durable and impressive patient responses, including complete remissions, when given for a fixed period of time. We believe these medicines could potentially transform treatment and offer new hope for people with lymphomas."

Pivotal Phase II Glofitamab Data Presented at ASH (Free ASH Whitepaper) 2022 and Published in NEJM

Updated data from the pivotal Phase II NP30179 study in people with R/R LBCL showed glofitamab given as a fixed course induced early and durable responses that were maintained beyond the end of treatment. Most patients who had achieved a complete response (CR; a disappearance of all signs of cancer) at the end of treatment experienced durable responses, with a median CR follow-up from end of treatment of 11.5 months (95% confidence interval [CI]: 10.5-16.4). Twelve months after the end of treatment with glofitamab, 61% of patients (n=37/61) maintained a CR, 92.6% remained progression-free, and only one patient (n=1/44) experienced disease progression.

Simultaneously, an earlier data cut from the Phase II NP30179 study in R/R diffuse large B-cell lymphoma (DLBCL) was published online in NEJM.

Data from this pivotal Phase II study have been submitted for review to the European Medicines Agency, and submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are ongoing.

Updated Pivotal Phase II Mosunetuzumab Data Presented at ASH (Free ASH Whitepaper) 2022

An updated analysis from the pivotal Phase II GO29781 study of mosunetuzumab in people with R/R FL who had received two or more prior therapies showed 60.0% (n=54/90; 95% CI: 49.1–70.2) achieved a CR and 77.8% (95% CI: 67.8–85.9) achieved an objective response (a CR or a partial response, a decrease in the amount of cancer in their body) at a median follow-up of 28.3 months. After 24 months of achieving a CR, 62.7% of patients remained in remission (95% CI: 37.7–87.7). Overall, 48.3% of patients remained progression-free (95% CI: 36.2-60.3). The median duration of response, median duration of CR, and median progression-free survival were not reached. Safety was consistent with the previous analysis of study data, with no new cytokine release syndrome (CRS) events or Grade 3 or higher adverse events (AEs) reported. CRS events were experienced by 44% of patients and were predominately low grade and during cycle one.

The European Commission granted conditional marketing authorization for mosunetuzumab for the treatment of people with R/R FL who have received at least two prior systemic therapies in June 2022, making it the first and only fixed-duration bispecific antibody to be approved in Europe for lymphoma. Mosunetuzumab is under Priority Review with the FDA, with a decision expected by December 29, 2022.

Additional Mosunetuzumab and Glofitamab Data Presented at ASH (Free ASH Whitepaper) 2022

Genentech continues to evaluate mosunetuzumab and glofitamab as part of its commitment to providing off-the-shelf therapies for people with lymphomas that can meet their diverse needs, including fixed-duration treatment options. Additional data presented at ASH (Free ASH Whitepaper) 2022 include the following:

A subcutaneous (SC) formulation of mosunetuzumab (administered as an injection given under the skin) demonstrated comparable efficacy with the intravenous formulation and a manageable safety profile in people with R/R non-Hodgkin’s lymphoma (NHL). The most common AEs were injection site reactions (60.9%; n=53/87) and CRS events (27.6%; n=24/87), which were all Grade 1 or 2. These findings suggest that a SC formulation of mosunetuzumab may offer patients a treatment option that could reduce their time spent in treatment centers.
Updated results from the Phase I/II G050554 study of mosunetuzumab monotherapy in elderly/unfit patients with previously untreated DLBCL and additional analyses from the Phase I/II G040516 study of mosunetuzumab in combination with Polivy (polatuzumab vedotin-piiq) in heavily pretreated people with DLBCL continued to show promising efficacy and manageable safety, highlighting the potential of mosunetuzumab in these patient populations.
Results from the Phase I/II NP30179 study evaluating glofitamab as a monotherapy following pretreatment with obinutuzumab in patients with heavily pretreated R/R mantle cell lymphoma continued to show early, high and durable response rates in this difficult-to-treat disease. After a median follow-up of eight months, the overall response rate (ORR) was 83.8%, with the majority of patients showing durable complete responses at the data cut off (74.1%; n=20/27). The most common AE was CRS (75.5%; n=28/37), with the majority low grade.
Data from the safety and expansion cohorts of the Phase Ib NP40126 study evaluating glofitamab in combination with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in patients with previously untreated DLBCL showed, after a median follow-up of 8.5 months, a best ORR of 92.7% (n=51/55) and a complete metabolic response rate of 72.7% (n=40/55). In the safety cohort, CRS events were all low grade (Grade 1 or 2 [10.7%; n=6/56]), and serious AEs were reported in 18 patients (32.1%).
Both mosunetuzumab and glofitamab are being investigated as SC formulations and in Phase III studies that will expand the understanding of their impact in earlier lines of treatment, with the aim of continuing to address the diverse needs and preferences of people with blood cancers. This includes the confirmatory Phase III CELESTIMO study investigating mosunetuzumab plus lenalidomide as a chemotherapy-free option for patients with R/R FL; the Phase III SUNMO study investigating mosunetuzumab plus Polivy versus rituximab in combination with gemcitabine plus oxaliplatin (R-GemOx) in patients with R/R aggressive B-cell NHL who are ineligible for autologous stem cell transplant (ASCT); and the Phase III STARGLO study evaluating glofitamab in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with R/R DLBCL who are ineligible for ASCT.

About Glofitamab

Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Glofitamab was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. A robust clinical development program for glofitamab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

About Mosunetuzumab

Mosunetuzumab is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for mosunetuzumab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

About Polivy (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy is designed to bind to CD79b on B cells and destroys them through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

On December 12, 2022 Orca Bio, a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, genetic blood disorders and autoimmune diseases, reported that interim clinical data from its Phase 1 multi-center trial of its second investigational cell therapy, Orca-Q, were unveiled in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Orca Bio, DEC 12, 2022, View Source [SID1234625184]).

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The data from the ongoing clinical trial show that Orca-Q reduced the incidence and severity of graft versus host disease (GvHD) and improved graft-versus-host disease-free, relapse-free survival (GRFS) rates in 26 patients matched to haploidentical allogeneic hematopoietic stem cell donors. Unlike standard of care haploidentical allogeneic hematopoietic stem transplant (alloHSCT), Orca-Q does not require post-transplant cyclophosphamide (PTCy).

"Patients and transplant physicians are in urgent need of a novel treatment option that improves the chances of survival and the quality of that survival. This is the key limitation of haploidentical transplant, which is currently the only treatment option for the vast majority of blood cancer patients in need of a transplant," said Amandeep Salhotra, M.D., associate professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. "These results suggest Orca-Q’s promise to overcome this serious challenge by offering a novel investigational high-precision cell therapy with the potential to significantly improve patient outcomes and reduce serious transplant-related risks."

Orca-Q is an investigational high-precision cell therapy that is a proprietary composition of enriched CD34+ stem cells combined with specific T cell subsets. The findings presented at ASH (Free ASH Whitepaper) are from patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS) and chronic myeloid leukemia (CML) who were matched to haploidentical allogeneic donors, defined as matched across at least 4/8 but fewer than 7/8 human leukocyte antigen (HLA) loci. Historical controls from the literature of patients who received standard of care haploidentical alloHSCT with PTCy GvHD prophylaxis were used for comparison purposes1,2,3,4.

Interim results from the Phase 1 single-arm, open-label trial showed:

A reduction of grade 2-4 acute GvHD (aGvHD) at 6 months as compared to literature controls (13% vs 21-63%), with only one patient developing grade 3 aGvHD and no incidence of grade 4 aGvHD.
No patients experienced moderate-to-severe chronic GvHD (cGvHD), compared to 24%-33% in the literature control. There was only one case of mild cGvHD.
GRFS was 75% at one year after Orca-Q, which compares favorably to a GRFS of 46% in patients in the literature control.
Patients treated with Orca-Q also experienced a low adverse event profile, suggesting Orca-Q has the potential to offer a new treatment option for patients undergoing haploidentical alloHSCT.

Today, approximately 70% of blood cancer patients do not have access to a fully matched related donor. Haploidentical transplant, which uses healthy, blood-forming cells from a partially matched donor to replace the unhealthy ones, is one of the few treatment options currently available to those without a fully matched donor. However, its use remains significantly limited because of the conditioning regimens that are required. Haploidentical transplant patients receiving higher intensity myeloablative conditioning treatments have a higher risk of cGvHD post-transplant, while patients receiving lower intensity pre-transplant conditioning have a greater risk of relapse.

"These interim results from our second clinical program demonstrate Orca-Q’s potential to overcome the challenges of haploidentical alloHSCT by providing a solution with which patients and physicians may no longer have to compromise between the risk of relapse and the risk of GvHD," said Scott McClellan, M.D., Ph.D., chief medical officer of Orca Bio. "This novel approach, along with our growing body of clinical evidence demonstrating Orca-T’s improved GvHD and relapse-free survival rates in patients with HLA-matched donors, underscore the potential of our high-precision platforms to deliver cell therapies that can greatly expand the number of patients who receive life-saving treatment, whether their donor is a full or partial match."

The full presentation will be made available on www.orcabio.com.

About Orca-Q
Orca-Q is Orca Bio’s second investigational high-precision allogeneic cellular therapy to enter clinical development for hematological malignancies. Orca-Q is a proprietary composition of enriched CD34+ stem cells combined with specific T cell subsets derived from haploidentical—or partially matched—donors that are purified through Orca Bio’s high-precision platform. Orca-Q is a first-in-class therapy that has the potential to improve patient outcomes and reduce the risks of graft versus host disease, without the use of post-transplant cyclophosphamide (PTCy) in patients for whom a full human leukocyte antigen (HLA) match cannot be found.

About Orca-T
Orca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and is being studied to treat multiple hematologic malignancies.