On May 31, 2023 Precision BioSciences, Inc. (Nasdaq: DTIL) a clinical stage gene editing company developing ARCUS-based in vivo gene editing and ex vivo allogeneic CAR T therapies, reported program updates across its allogeneic CAR T pipeline. The Company highlighted new interim clinical data for its lead candidate, azercabtagene zapreleucel (azer-cel), as a potential first-in-class allogeneic CD19 CAR T for the growing CAR T relapsed patient population with DLBCL (Press release, Precision Biosciences, MAY 31, 2023, View Source [SID1234632283]). The Company also provided the first clinical update on PBCAR19B stealth cell, which is in development as a potential best-in-class allogeneic CAR T therapy for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL), with primary focus on DLBCL.

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"Over the last two years, we have pursued a deliberate, multi-faceted approach in the development of our CAR T programs with the aim of bringing off-the-shelf therapies to patients. In the process, we have built one of the most extensive data packages for an allogeneic product, with the goal of tailoring azer-cel for patients who have relapsed following autologous CAR T treatment," said Michael Amoroso, Chief Executive Officer at Precision BioSciences. "With the updated clinical data presented today, including safety, efficacy, and durability, we believe we have identified the recommended azer-cel dosing regimen to discuss in a clinical meeting with the U.S. Food and Drug Administration (FDA) to align on next steps."

Mr. Amoroso continued, "In addition to azer-cel, we are also advancing our CD19-targeted program, PBCAR19B stealth cell, which incorporates an immune cloaking approach designed to allow greater CAR T expansion and persistence. Last year, we applied platform-wide manufacturing optimizations using ARCUS for CAR T insertion for both of our clinical candidates. We believe the optimized stealth cell product resulted in preliminary efficacy and safety on par with autologous CAR T in the r/r DLBCL setting. The interim data highlighted today supports further investigation of the stealth cell product candidate in DLBCL patients. Looking ahead, we will continue to evaluate the durability of response in the stealth cell patients and seek potential partnerships in this larger, earlier line setting."

Azer-cel as a Potential First-in Class Allogeneic CAR T Product Candidate for CD19+ CAR T Relapsed Patients

As of May 30, 2023, we observed continued high response rates with an acceptable safety profile in r/r NHL patients. Among all evaluable subjects (n=61), ORR was 58% with 41% achieving a CR, across all doses and lymphodepletion regimen.

Activity was most compelling among the azer-cel treated subjects who had relapsed following autologous CAR T therapy (n=18); ORR was achieved in 83% of subjects and 61% achieved CR.
In CAR T relapsed evaluable subjects (n=11), 55% had ongoing durable responses for ≥ 6-months.
In the most recent CAR T relapsed cohort receiving optimized Dose Level 4b with FluCy7501 (n=5), 60% ORR was achieved, and 66% of evaluable patients achieved a full molecular remission (MRD-) which may be predictive of durability.
No Grade 3 or greater cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection or graft versus host disease was observed in the most recent cohort.
"Azer-cel continues to demonstrate promising results in DLBCL patients who relapsed following CAR T, and we are encouraged by the high overall response rates with molecular remissions in this patient setting," said Alan List, M.D., Chief Medical Officer at Precision BioSciences. "Based on this dataset, azer-cel has the potential to improve outcomes in this large and growing population with high unmet need. Also based on these results, a clinical meeting with the FDA has been scheduled in June to discuss next steps for azer-cel in the CAR T relapsed setting. We look forward to providing updates on the path forward in the near future."

PBCAR19B Stealth Cell as a Potential Best-in Class Allogeneic CAR T Product Candidate for Earlier Line CAR T Naïve CD19+ DLBCL

PBCAR19B is Precision’s anti-CD19 targeting allogeneic CAR T candidate designed to evade immune rejection by host T cell and NK cells with a single ARCUS gene edit to insert a CD19 CAR transgene, knock-down beta-2 microglobulin, and insert an HLA-E transgene. The treatment goal of this program is to potentially displace autologous CAR T in the 2nd line DLBCL setting.

As of May 30, 2023, in Phase 1 results we observed an acceptable safety profile with high overall response rates among all evaluable subjects with evidence of molecular remission (MRD-) and preliminary durability at Dose Level 2 (540 million cells)2.

Out of seven evaluable subjects at Dose Level 2, five with DLBCL and two with mantle cell lymphoma, PBCAR19B achieved 71% ORR and 43% CR rate.
In DLBCL patients, ORR was achieved in 80% of subjects and 60% achieved a CR (MRD-).
No Grade 3 or greater cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection or graft versus host disease was observed.
PBCAR19B stealth cell achieved proof of concept and appeared to be effective in delaying recovery of host T- and NK-cells.
PBCAR19B stealth cell dosed at 540M cells + FluCy750 has been established as the dosing regimen for further investigation in DLBCL patients.
"We are impressed with our PBCAR19B stealth cell construct which appeared to delay host rejection through immune cloaking. Stealth cell achieved a high response rate, especially in DLBCL subjects with a high frequency of MRD- complete responses, and acceptable safety with our improved manufacturing process at Dose Level 2 in the Phase 1 study," said Dr. List. "The next steps for stealth cell will be to await further durability data and seek thoughtful partnership for ongoing development in the earlier line DLBCL setting."

Company-Hosted Webcast and Conference Call Information

Precision will host a conference call and webcast today, May 31, 2023, at 8:30 AM ET. The dial-in conference call number is (800) 715-9871 and the conference ID number for the call is 4729500. Participants may access the live webcast, and accompanying presentation materials, as well as the archived webcast on Precision’s website in the Investors section under Events & Presentations: View Source

On May 31, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in a fireside chat at the Jefferies Healthcare Conference on Wednesday, June 7, 2023, at 10:00 a.m. ET (Press release, ORIC Pharmaceuticals, MAY 31, 2023, View Source [SID1234632282]).

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The live webcast of the discussion will be available through the investor section of the company’s website at www.oricpharma.com. A replay of the webcast will be available for 90 days following the event.

On May 31, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that Dr. James Breitmeyer, Oncternal’s President and Chief Executive Officer will present at the 2023 Jefferies Healthcare Conference (Press release, Oncternal Therapeutics, MAY 31, 2023, View Source [SID1234632280]).

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2023 Jefferies Healthcare Conference
Date: Wednesday, June 7, 2023 at 4:30pm (ET) in Track 7

During the conference, Dr. Breitmeyer and members of Oncternal’s management team will conduct one-on-one meetings with registered investors.

The webcast will be available online at investor.oncternal.com, for at least 30 days after the event.

On May 31, 2023 OncoNano Medicine, Inc. reported that it will present positive final results from its Phase 2 study of pegsitacianine, a pH-sensitive fluorescent nanoprobe for enhanced intra-operative visualization of cancer, in a podium presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023 (Press release, OncoNano Medicine, MAY 31, 2023, View Source [SID1234632279]). Results of the study show that acidic pH is a viable marker and can be used for tumor targeting by the company’s ON-BOARD micelle platform.

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Pegsitacianine has been studied in more than 135 patients across multiple tumor types, including peritoneal metastatic, breast, head and neck, colorectal, esophageal, ovarian and prostate cancers. Results show that pegsitacianine is able to localize different tumor types regardless of their histology or anatomic location. The ON-BOARD platform, therefore, is able to target solid tumors, deploying its payload specifically within the acidic tumor microenvironment (TME).

"We are encouraged by this data as it demonstrates the potential of pegsitacianine to augment the visualization of cancer during an operation, which has the potential to be a significant advance in real-time surgical imaging," said Kartik Krishnan, M.D., Ph.D., Chief Medical Officer of OncoNano Medicine. "We look forward to taking pegsitacianine to the next levels of development and continue our mission to diagnose and treat cancer with high specificity."

The results of this Phase 2 study reveal that pegsitacianine was well tolerated and that 20 of 40 evaluable patients (50%) had pathology-confirmed disease resected, that was not resected in the planned standard of care surgery, under pegsitacianine guidance. Approximately 25% of patients experienced a pegsitacianine-related adverse event, which was a transient, selfresolving, non-anaphylactic infusion-related reaction.

"We were highly encouraged with the results observed in this Phase 2 trial and look forward to validating these findings in the upcoming Phase 3 trial," said Patrick Wagner, M.D., lead author and Director of Complex General Surgical Oncology, Allegheny Health Network Cancer Institute. "The results demonstrate that acidic pH is a viable tumor agnostic marker and highlight pegsitacianine’s ability to target different tumor types regardless of their genotype or anatomic location."

"This Phase 2 data brings new hope to both clinicians and patients," said Charles M. Balch, M.D., former EVP and Chief Executive Officer of ASCO (Free ASCO Whitepaper) and present Chair of the Scientific Advisory Board at OncoNano Medicine. "Having demonstrated the capacity to identify tumors that were previously not clinically visible to surgeons, pegsitacianine has the potential to improve the accuracy of staging and surgical outcomes, while reducing operating time for several types of abdominal cancers. Newer versions in the pipeline have great potential to expand therapeutic targets and enable new combinations of drugs previously hindered by toxicity."

Presentation Overview:

TITLE: Detection of peritoneal metastases during cytoreductive surgery using pegsitacianine, a pH sensitive imaging agent: Final results from a phase 2 study
PRESENTER: Patrick Wagner, MD, Director of Complex General Surgical Oncology, Allegheny Health Network Cancer Institute
DATE: June 5, 2023

On May 31, 2023 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported pre-clinical data from the Company’s multiple tumor-associated antigens (multiTAA)-specific T cell product candidate MT-601 in lymphoma cells, including CD19 CAR T refractory cells (Press release, Marker Therapeutics, MAY 31, 2023, View Source [SID1234632278])`.

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Although CAR T cell therapies targeting the CD19 antigen have gained acceptance as treatment for patients with relapsed/refractory lymphoma because of their significant benefit relative to the standard of care, up to 60% of patients treated with CAR T therapies relapse within a year (Chong EA et al, N Engl J Med, 2021).

MultiTAA-specific T cell therapy was investigated in the Baylor TACTAL study, which enrolled patients with both Hodgkin’s and non-Hodgkin’s lymphoma (Vasileiou et al, J Clin Oncol, 2021). The multiTAA-specific T cell product used in the TACTAL study was directed against five antigens and showed more durable clinical responses. For example, some patients who attained a complete remission (CR) with the multiTAA-specific T cell treatment were still in remission at the 72 months follow-up, suggesting a longer-lasting clinical benefit relative to published results for CD19 CAR T therapies.

Given the high probability of antigen-loss associated relapse seen with CD19 CAR T therapy, Marker believes that its multiTAA-specific T cell product may result in durable responses due to its ability to overcome antigen loss by targeting more than one antigen. Data from the TACTAL study has demonstrated that multiTAA-specific T cell products recognize cancer cells by up to five antigens presented on cancer cells and continue to kill even when cancer cells morph by downregulating the targeted antigen to escape recognition.

Marker recently started to evaluate the safety and efficacy of MT-601, a multiTAA-specific T cell product that recognizes six antigens, including WT-1, a TAA that was not part of the targeted antigens in the TACTAL study, in patients with non-Hodgkin’s lymphoma who have either relapsed after receiving anti-CD19 CAR T cell treatment or are ineligible for anti-CD19 CAR T cell treatment (ClinicalTrials.gov Identifier: NCT05798897). Marker believes that killing induced by a product directed against six TAAs instead of five TAAs can potentially provide a more durable solution. Prior to starting the clinical trial Marker assessed the killing capacity of MT-601 in vitro in a lymphoma cell line and demonstrated that MT-601 kills lymphoma cells regardless of their CD19 expression levels.

"We have recently developed a long-term in vitro model to monitor the interaction of T cells with cancerous cells. Data from a lymphoma cell line utilizing this model demonstrated that MT-601 inhibited growth of lymphoma cells as well as the growth of CD19 CAR resistant lymphoma cells," said Eric A. Smith, Ph.D., Director of Research and Development at Marker Therapeutics. Marker has posted further details about this preclinical study on the Investor Relations section of its website.

Dr. Smith continued "Specifically, we have developed an in vitro model which reproduces the CD19 antigen-negative tumor that causes relapse and observed the following:

· In this in vitro model, 98% of lymphoma cells were eliminated after initial administration of a CD19-targeting CAR T cell product.
· While the CAR T cells significantly controlled lymphoma cell growth, we observed that 3 weeks after the start of anti-CD19 CAR T cell administration, a population of lymphoma cells that were resistant to CD19 CAR T cell administration started to grow.
· These CD19 CAR resistant lymphoma cells were tested for CD19 expression and were shown to be negative for the CD19 surface antigen, which explained why they were no longer controlled with a second administration of anti-C19 CAR T cells, thus recapitulating the antigen-negative relapse observations in CAR relapsed/refractory lymphoma patients.
· However, when MT-601, with its broad antigen recognition (Survivin, NY-ESO-1, WT-1, PRAME, MAGE-A4, SSX2) was added to this anti-CD19 CAR T cell resistant cell population complete growth inhibition was observed.

These data highlight that MT-601 has the potential to eliminate tumors that are CD19 CAR T cell refractory, indicating that MT-601 might offer a viable therapeutic option for lymphoma patients that have relapsed from previous CAR T cell interventions."

"We are encouraged by the promising results of our pre-clinical study of MT-601," said Juan F. Vera, M.D., President and Chief Executive Officer at Marker Therapeutics. "These pre-clinical findings reinforce previous TACTAL clinical observations, highlighting the potential benefit of our innovative multiTAA-specific T cell therapy in CD19 CAR T refractory lymphoma patients. Our Investigational New Drug (IND) application for MT-601 for the treatment of patients with relapsed non-Hodgkin lymphoma has been cleared by the FDA and we are excited to further explore the potential benefits of MT-601 in our multicenter Phase 1 clinical trial, which was initiated in the first quarter of 2023. We are continuing our detailed review of the scope of clinical opportunities provided by MT-601 and look forward to providing an update about our clinical strategy and anticipated milestones as soon as possible."

About multiTAA-specific T cells

Marker’s multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 180 patients with various hematological malignancies and solid tumors showed that the multiTAA-specific T cell product was well tolerated, demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the patient’s own T cells to expand, potentially contributing to a lasting anti-tumor effect. Unlike other cell therapies which require hospitalization and close monitoring, multiTAA-specific T cells are designed to be administered in an outpatient setting.