On April 8, 2022 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported that it will present preclinical data on bbT369, an investigational novel CD79a/CD20 dual-targeting CBLB gene edited CAR T cell therapy at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 in New Orleans, LA (Press release, 2seventy bio, APR 8, 2022, View Source [SID1234611707]). These data will be presented in a poster session (poster #581) on Sunday, April 10, 1:30-5:30 PM CT.

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"While anti-CD19 CAR T cell therapies have improved outcomes for relapsed and/or refractory B cell non-Hodgkin lymphoma (B-NHL) patients, 60-70% of those treated with currently available CAR T cell therapies do not achieve a long-term remission, highlighting the need for more treatment options," said Philip Gregory, D.Phil., chief scientific officer at 2seventy bio. "bbT369 was purposefully designed to potentially address known mechanisms of anti-CD19 CAR T cell therapy failure. We are excited to present the results of preclinical studies that demonstrate the anti-lymphoma activity of bbT369 and suggest that bbT369 has the potential to overcome failure modes of anti-CD19 CAR therapies, supporting a first-in-human trial (CRC-403) to evaluate initial safety and efficacy in B-NHL patients."

bbT369 is an innovative therapeutic approach designed to address known limitations of anti-CD19 CAR T cell therapy

Emerging data1-2 suggests several failure modes for anti-CD19 CAR T cell therapies, including loss or down-regulation of CD19 antigen, loss of co-stimulatory ligands on tumor cells, exhaustion of CAR T cells, and immunosuppressive microenvironments.

bbT369 was purposely designed with three layers of innovation to address the potential mechanisms of anti-CD19 CAR T cell therapy failure:

First, bbT369 targets a novel combination of antigens highly expressed in B cell lymphomas, CD79a and CD20. CD79a, a novel target, is a critical signaling component of the B cell receptor and CD20 is a known clinical target for lymphoma. The dual targeting of bbT369 may limit antigen escape as a mechanism of lymphoma relapse.
Second, bbT369 is designed with a combination of a traditional 2nd generation CAR and an investigative "chimeric co-stimulatory" architecture (CCR-CAR), a split co-stimulation signaling technology intended to drive more robust T cell activation in response to either antigen compared with dual CAR designs.
Third, cells are gene-edited with megaTAL technology to remove the function of CBLB, a known negative regulator of T cells. Removal of CBLB function may enable robust antigen-dependent CAR T cell expansion and allow cells to resist anergy and maintain activity in sub-optimal conditions for T cell activation.
bbT369 demonstrates increased anti-lymphoma activity and duration of response in preclinical models

Increased tumor control was seen with bbT369’s CCR-CAR design compared to dual CAR designs, and cell killing was observed when bbT369 encountered either antigen.
Compared with non-gene edited cells in different in vitro model systems, bbT369 demonstrated a lower threshold for stimulation, retained activity in the presence of the immunosuppressive factor TGFβ, reduced reliance on tumor cell co-stimulation, and exhibited increased capacity for multiple rounds of tumor cell killing.
bbT369 resulted in three-fold increased cell expansion and prevention of late relapses in B-NHL mouse models compared with a non-gene edited control.
bbT369 outperformed CD19 CAR T cells in cell-based and mouse models, with increased IL-2 secretion and prolonged duration of tumor remission, suggesting bbT369 may have enhanced functionality compared with the other constructs.
Results are detailed in an E-Poster here, available to registered attendees on the AACR (Free AACR Whitepaper) website through Wednesday, July 13.

Infusion of first patients in Phase 1/2 study of bbT369 in B-NHL is anticipated in 2022

CRC-403 (NCT05169489), an open-label, multi-site Phase 1/2 dose-escalation study, is currently enrolling patients, and will assess the safety and potential efficacy of bbT369 in patients with relapsed and/or refractory B-NHL, including patients who relapsed after CD19 CAR T cell therapy as well as patients who are CAR-naïve. Initial assessment of feasibility of bbT369 drug product manufacturing and patient safety is expected in 2H 2022.

The study will also serve as a proof-of-concept assessment of 2seventy bio’s proprietary megaTAL gene editing platform, dual-targeting strategies and split co-stimulation signaling technology.

About bbT369

bbT369 is an investigational dual-targeting CAR T cell therapy with a gene edit for patients with relapsed and/or refractory B-NHL.

bbT369 has three layers of innovation, purposely designed to address the potential mechanisms of anti-CD19 CAR T cell therapy failure: dual targeting (CD79a/CD20), split co-stimulation signaling technology, and a gene edit to remove the function of CBLB.

In December 2021, the FDA cleared the Investigational New Drug (IND) application for bbT369.

The clinical development program for bbT369 includes the Phase 1/2 CRC-403 study (NCT05169489). Safety and potential efficacy of bbT369 in patients with specific subtypes of relapsed and/or refractory B-NHL will be assessed, including patients who relapsed after CD19 CAR T cell therapy as well as patients who are CAR-naïve.

bbT369 is not approved for any indication in any geography.

About megaTAL technology

megaTALs are single-chain enzymes that combine the natural DNA recognition and cleavage processes of Homing Endonucleases (HEs) with the modular DNA binding properties of transcription activator-like (TAL) effectors. This protein fusion architecture allows the generation of highly specific and active nucleases in a compact format compatible with all current viral and non-viral cell delivery methods.

On April 8, 2022 Kiromic BioPharma, Inc. (NASDAQ: KRBP) ("Kiromic" or the "Company"), a clinical-stage fully integrated biotherapeutics company using its proprietary DIAMOND artificial intelligence (AI) and big data mining platform to discover and develop cell and gene therapies with a therapeutic focus on immuno-oncology, reported financial results for the fourth quarter and fiscal year ended December 31, 2021 (Press release, Kiromic, APR 8, 2022, View Source [SID1234611706]).

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"We are extremely encouraged by the progress the Company demonstrated in the fourth quarter. Our team’s unified efforts are strictly focused on achieving our goal of beginning the activation of the clinical trial for our first oncology cell therapy candidate by the end of the fourth quarter of 2022," stated Pietro Bersani, Kiromic BioPharma’s Interim Chief Executive Officer. "We have been intensely preparing for this milestone, ensuring we have the right team, the right capabilities, and the right processes in place to achieve this objective. Our team has been executing critical advancements – occurring simultaneously – across our research and development, clinical trial preparation, facility expansion, and manufacturing operations, among other functions. We look forward to more opportunities to communicate with our shareholders as we demonstrate the Company’s overall progress."

Fiscal Year Ended 2021 Financial Highlights:

Cash Position: Cash and cash equivalents were $25,353,900 as of December 31, 2021, compared to $10,150,500 as of December 31, 2020. The difference is attributable to cash outflows of $20,321,500, and $1,810,800 for operating activities, and investing activities, respectively. There were cash inflows of $37,335,700 from financing activities.
R&D Expenses: Our research and development expenses increased by $6,314,900, or 124.98%, to $11,367,800 for the year ended December 31, 2021 from $5,052,900 for the year ended December 31, 2020. The increase was attributable to increased headcount, manufacturing, and experimentation costs for the development of our ALEXIS clinical platform.
G&A Expenses: Our general and administrative expenses decreased by $206,100, or 1.46%, to $13,937,900 for the year ended December 31, 2021 from $14,144,000 for the year ended December 31, 2020. This decrease was primarily due to reduced stock compensation expenses, offset by increases in professional services fees, personnel, and recruiting costs.
Net Loss: Our net loss increased to $25,588,700 during the year ended December 31, 2021 compared to $19,200,200 during the year ended December 31, 2020.
Recent Business Highlights:

ALEXIS (Gamma Delta CAR-T cell Platform) Research & Development:

Developed an innovative and highly efficient process that improves the manufacturing of our cell therapy candidates, making it more space-efficient and cost-effective. We believe that this will significantly reduce the costs of CAR-T cell manufacturing, providing a competitive market advantage.
Successfully tested a prototype variant of the ALEXIS manufacturing process that leverages the potential of pooled donors’ cells. This is a necessary step to building a proprietary bank of precursor cells for the manufacturing of our ALEXIS product line. A donor cell bank is expected to ensure a high degree of homogeneity and consistency of our drug products, and at the same time to improve the resilience of our supply chain.
Continued progress towards a scalable and retrovirus-free process for the delivery of recombinant genes into T cells. This is an important step towards the deployment of our proprietary non-viral cell engineering system.
Key Hires in Research & Development, Clinical Translational Medicine and Clinical Trial Preparation:

The Company added new hires across the organization, specifically augmenting research & development, clinical translational medicine and clinical trial preparation capabilities. This represents a headcount total of nearly 60 employees, which is an increase from 19 as of December 31, 2020.
cGMP Manufacturing:

We have completed approximately 90% of our in-house current Good Manufacturing Practices (cGMP) facility expansion and redesign.
DIAMONDAI 2.0 Platform for Drug Discovery and Development is Completed:

The Company developed and made operational a completely revised version of its proprietary platform for identification and vetting of immunotherapy targets. Diamond AI 2.0 was developed by Kiromic’s in-house bioinformatics team and includes:
Enhanced and updated existing models to provide more accurate predictions of therapy target efficacy;
A modular, containerized architecture to support rapid addition of new algorithms, scientific methods, and therapy designs;
Integrated data mining components to provide a seamless workflow from identification of cancer-specific surface protein regions through to vetted immunotherapy targets;
Proteomic validation of transcript targets;
An additional 300+ million data points were added to the DIAMOND database in Q4 2021, which included proteomic data covering and extending the range of cancer types; and
Approximately 600 million data points were added in 2021, representing a 50% data point increase from 2020.

On April 8, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that the company will present a poster at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, which is being held April 8-13, 2022, in New Orleans, La., and virtually (Press release, Cytori Therapeutics, APR 8, 2022, View Source [SID1234611705]).

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Details of the poster presentation

Title: A biology-based, mathematical model to predict the response of recurrent glioblastoma to treatment with 186Re-labeled nanoliposomes

Session Title: Mathematical Models

Session Date and Time: Tuesday, April 12, 2022, 9:00 a.m. – 12:30 p.m. CT

Location: New Orleans Convention Center, Exhibit Halls D – H, Poster Section 29

Poster Board Number: 13

Permanent Abstract Number: 2742

Link to Abstract: View Source!/10517/presentation/18391

A copy of the poster presentation will be made available under the Presentations tab of the For Investors section of the Company’s website following the meeting at www.plustherapeutics.com.

On April 8, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported updated clinical data and new biomarker analyses from its ongoing Phase 2 trial of onvansertib in combination with abiraterone/prednisone in metastatic castrate-resistant prostate cancer (mCRPC) patients (Press release, Cardiff Oncology, APR 8, 2022, View Source [SID1234611704]). The data are featured in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans, Louisiana from April 8-13, 2022.

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"Results from the mCRPC trial demonstrate clinically meaningful disease control rates in patients showing early resistance to abiraterone," said David Einstein, M.D., principal investigator at Beth Israel Deaconess Medical Center. "As the dose density of onvansertib was increased in three consecutive Arms (A, B and C), we observed an increase in disease control rates with both PSA stabilization and radiographic stable disease twelve weeks into treatment and some of these patients have experienced durable stabilization. Pre-clinical data suggest that the synergistic effect is independent of androgen receptor signaling."

The primary efficacy endpoint of the mCRPC trial is disease control rate at 12 weeks (12-week DCR), which is defined by a decline or stabilization of PSA levels (rise of <25% over baseline or less than 2 ng/mL). Each of the trial’s three arms has evaluated a different dosing schedule of onvansertib alongside abiraterone and prednisone administered throughout the respective treatment cycle. Arm A evaluated 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, Arm B evaluated 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, and Arm C is evaluating 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles.

"Biomarker correlative studies have revealed significant and positively associated mutations in MTOR, FAT1, PTEN and FOXA1, with tumors harboring these mutations achieving stable disease or a partial response within the initial abiraterone-resistant setting," said Tod Smeal, Ph.D., chief scientific officer of Cardiff Oncology. "In addition, gene expression signatures from patient tumor tissue biopsies correlated with treatment response included those corresponding to the ERG+ and Notch pathways, which are involved in cell-invasion, epithelial-mesenchymal transition and metastasis. We continue to examine these promising biomarker studies with the goal of identifying the genomic alterations most closely associated with response to the combination regimen of onvansertib and abiraterone."

Key data and conclusions from the AACR (Free AACR Whitepaper) poster (cut-off date of February 2, 2022) and ongoing trial include:

Efficacy:

75% (15/20) of evaluable patients in Arm C, which represents the most dose dense treatment schedule, showed disease control by radiographic SD/PR at 12-weeks, compared to 53% (9/17) and 58% (11/19) in the less dose dense Arms A and B, respectively
Biomarker:

Treatment response (SD/PR) was positively associated with mutations in PTEN and MTOR, key genes in the PI3K signaling pathway
Gene signatures correlating with treatment response included those corresponding to the ERG+ and Notch pathways, which are involved in cell-invasion, epithelial-mesenchymal transition and metastasis
Genes related to mitochondrial and immune functions were downregulated in patients achieving SD or a PR compared to those showing progressive disease
Safety:

The treatment regimen of onvansertib in combination with abiraterone/prednisone has been well tolerated
An electronic copy of the poster and corresponding abstract, entitled, Biomarkers of response to abiraterone and the polo-like kinase 1 (PLK1) inhibitor onvansertib in metastatic castration resistant prostate cancer (mCRPC) patients, is available to registered attendees of the AACR (Free AACR Whitepaper) annual meeting on the meeting website. The in-person presentation will take place during the "Biomarkers Predictive of Therapeutic Benefit 1" poster session on April 11, 2022, from 9:00 AM – 12:30 PM CT. Following the meeting, the poster will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

On April 8, 2022 Seagen Inc. (Nasdaq: SGEN) reported that a jury in the U.S. District Court for the Eastern District of Texas found that Daiichi Sankyo Co. Ltd. ("Daiichi Sankyo") infringed Seagen’s U.S. Patent No. 10,808,039 by selling in the United States its Enhertu product (trastuzumab deruxtecan; DS-8201) (Press release, Seagen, APR 8, 2022, https://investor.seagen.com/press-releases/news-details/2022/Seagen-Announces-Jury-Award-in-Patent-Infringement-Case-Against-Daiichi-Sankyo/default.aspx [SID1234611703]). Seagen was awarded damages of $41.82 million for past infringement of the patent. In addition, Seagen will request additional royalty payments for future sales of Enhertu in the United States through the life of the patent.

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"We are pleased that the jury recognized the validity of asserted claims of our patent and found that Daiichi Sankyo willfully infringed our proprietary technology without permission," said Clay Siegall, Ph.D., President and Chief Executive Officer, Seagen. "As a pioneer and leader in antibody-drug conjugate (ADC) technology, protecting our intellectual property is essential to our ability to continue developing innovative therapies for cancer patients in need."

In addition to the damages the jury awarded for past infringement, Seagen will request the court to award a royalty on Daiichi Sankyo’s future sales in the United States of Enhertu until patent expiry in November 2024. The court will determine the amount of these payments in a decision Seagen anticipates later this year.

In a related matter, on April 7, 2022, the Patent Trial and Appeal Board of the U.S. Patent and Trademark Office granted a request on rehearing and instituted two post grant review (PGR) proceedings brought against certain claims of U.S. Patent No. 10,808,039. Seagen intends to vigorously defend the patent in the PGRs.

Separately, Seagen is engaged in an arbitration it brought against Daiichi Sankyo over ownership of certain technology used by Daiichi Sankyo in trastuzumab deruxtecan and several other drug candidates. In the arbitration, which remains ongoing, Seagen contends that the linker and other ADC technology used in these compounds are improvements to Seagen’s pioneering ADC technology, the ownership of which is automatically assigned to Seagen under the 2008 collaboration agreement between Daiichi Sankyo and Seagen. A decision in the arbitration case is expected by mid-2022.