On April 19, 2023 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported data on WU-NK-101, the company’s lead memory natural killer (NK) cell therapy product, in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, Florida from April 14 – 19, 2023 (Press release, Wugen, APR 19, 2023, View Source [SID1234630319]).

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"These data build on the growing body of evidence demonstrating the broad, powerful immuno-oncology applications of WU-NK-101," said Kumar Srinivasan, Ph.D., M.B.A., President and Chief Executive Officer of Wugen. "In addition to our ongoing efforts to advance WU-NK-101 for AML and colorectal cancer, we plan to explore WU-NK-101 as a salvage therapy for patients who have failed or are resistant to immune checkpoint blockade treatment, given the tremendous need and lack of options in this population."

"WU-NK-101 has a unique phenotype that supports enhanced cytotoxicity, metabolic fitness and flexibility, and resistance to immunosuppression within the TME," added Sergio Rutella, M.D., Ph.D., FRCPath, FRSB, Professor of Cancer Immunotherapy at Nottingham Trent University, and a co-author of the study. "Today’s findings further enhance WU-NK-101’s anti-tumor profile, showing that these cells can also enhance the adaptive immune response in the TME, upregulate key checkpoints, and potentially increase cytotoxicity in combination with checkpoint inhibitors. These findings are extremely promising and suggest a synergistic effect when combining WU-NK-101 with CPI antibodies to treat solid tumors."

Today’s presentation highlighted the following:

Cytokine-induced memory-like (CIML) NK treatment in relapsed/refractory acute myeloid leukemia (AML) patients was associated with high cytotoxic T lymphocyte (CTL) infiltration and led to modifications in the tumor microenvironment (TME) towards a more T-cell amenable environment in solid tumors.
CIML-NK cell infiltration positively and significantly correlated with an abundance of activated T cells and with dendritic cell infiltration, suggesting coordinated changes in immune cell populations within the TME after treatment.
PD-L1 and MHC-I checkpoint upregulation by WU-NK-101 was confirmed in in vitro and in vivo solid tumor models.
In in vitro models, WU-NK-101 secreted factors augmented PD-L1 and MHC-I expression, with a dose-dependent increase observed.
In vivo xenograft models confirmed the efficacy of WU-NK-101 as a monotherapy and confirmed in vitro findings of increased checkpoint expression post-treatment.
The combination of WU-NK-101 with checkpoint inhibitor (CPI) antibodies enhanced cytotoxicity in vitro.
WU-NK-101 has the potential to reverse the primary and acquired mechanisms of immune checkpoint blockade resistance.
The details of Wugen’s presentation at AACR (Free AACR Whitepaper) are as follows:

Title: WU-NK-101 as Salvage Therapy Post Immune Checkpoint Blockade (ICB)

Abstract Number: 6418

Date and Time: Wednesday, April 19, 2023, 9:00 a.m. – 12:30 p.m. ET

Location: Section 25

Additional meeting information can be found at View Source

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

On April 19, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that Mark Rothera, its President and Chief Executive Officer, and Lisa Rojkjaer, M.D., its Chief Medical Officer, are scheduled to participate in a virtual fireside chat at the Stifel 2023 Targeted Oncology Days on Wednesday, April 26, 2023, at 12:00 p.m. ET (Press release, Viracta Therapeutics, APR 19, 2023, View Source [SID1234630318]).

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A live webcast of the fireside chat will be available on the Investors section of the Viracta website under "Events and Webcasts" and archived for 90 days.

On April 19, 2023 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster of VIP924 preclinical data at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Vincerx Pharma, APR 19, 2023, View Source [SID1234630317]).

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VIP924 consists of an anti-CXCR5 humanized monoclonal antibody with a novel linker containing a unique peptide sequence specifically cleaved by legumain—a tumor-associated lysosomal protease. Inside the tumor cell, upon legumain cleavage, the active payload, VIP716, is released. VIP716 is a novel highly potent and selective kinesin spindle protein inhibitor (KSPi), which has been modified with a hydrophilic CellTrapper moiety to reduce membrane permeability without having a negative impact on efficient target binding. This modification allows for intracellular accumulation of VIP716 in CXCR5+ tumor cells, providing greater efficacy, and prevents cellular penetration into healthy tissues, reducing toxicity.

"We are thrilled to continue advancing our bioconjugation platform with our newest ADC, VIP924," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "At AACR (Free AACR Whitepaper), VIP924 showed meaningful preclinical activity in a panel of lymphoma cell lines and in cell line-derived and patient-derived lymphoma mouse models. Most notably, mouse models implanted with tumor cells from lymphoma patients demonstrated significant tumor growth inhibition and prolonged survival after VIP924 treatment. Showing activity in mouse models implanted with tumor cells from patients, also known as PDX models, is particularly meaningful because PDX models are more representative of the complexity of human cancer than results seen with cell lines."

Dr. Hamdy continued, "Despite progress in the treatment of B-cell malignancies, there is still an unmet medical need, especially for patients with relapsed or refractory disease. The results presented at AACR (Free AACR Whitepaper), together with our previous efficacy findings of durable complete tumor regression in CXCR5-positive, ibrutinib-refractory lymphoma models, suggest that VIP924 has the potential to be a treatment option for relapsed and refractory patients. Looking at the totality of preclinical data we’ve generated, including the data we presented at ASH (Free ASH Whitepaper) that showed how our next generation linker, payload, and CellTrapper technology significantly improved the safety and efficacy of the approved ADC, Mylotarg, we can’t help but be excited about the future of our ADC programs. We look forward to filing the IND for VIP924 in mid-2024."

Key Presentation Highlights:
Poster presentation, titled, CXCR5 is a very promising drug target for the development of antibody-drug conjugates to treat patients with lymphoma, presented by Tibor Schomber, Ph.D., Vincerx Pharma GmbH, Monheim, Germany, include:

High expression of CXCR5 was observed by immunohistochemistry on naive and previously treated diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL) samples; with limited expression in healthy tissues.
VIP924 showed superior in vitro cytotoxicity across different non-Hodgkin lymphoma cell lines compared with other B-cell lymphoma targeting antibodies conjugated to the same effector chemistry including, CD19-KSPi, CD22-KSPi, and CD70-KSPi.
VIP924 (10mg/kg) resulted in significant tumor growth inhibition in two DLBCL patient-derived tumor models: 68% in a low CXCR5-expressing model and 87% in a high CXCR5-expressing model. Prolonged survival of VIP924-treated animals was observed in both models. No effect on body weight or any adverse effects in the VIP924-treated mice were observed.
To determine the efficacy of VIP924 in large, established tumors, a single VIP924 dose of 10mg/kg was administered in mice transplanted with the HBL-1 lymphoma cell line. Complete responses were observed in 2 out of 3 mice with no measurable tumors on treatment day 26. After 24 and 48 hours, accumulation of VIP716 (ie, payload; "metabolite") was observed in the tumors but not in plasma.
KSP inhibition resulted in mitotic arrest and the formation of characteristic monopolar spindles (monoasters). VIP924 treatment produced higher levels and longer duration of monoaster formation in a lymphoma cell line compared to the permeable, small molecule KSPi, ispinesib.
The poster can be accessed on the presentations section of the Vincerx website.

On April 19, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultra-rare diseases, reported the grant of non-qualified stock options to purchase an aggregate of 11,035 shares of common stock of the company and 17,710 restricted stock units of the company’s common stock to 11 newly hired non-executive officers of the company (Press release, Ultragenyx Pharmaceutical, APR 19, 2023, View Source [SID1234630316]). The awards were approved by the compensation committee of the company’s board of directors and granted under the Ultragenyx Employment Inducement Plan, with a grant date of April 16, 2023, as an inducement material to the new employees entering into employment with Ultragenyx in accordance with Nasdaq Listing Rule 5635(c)(4).

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The restricted stock units vest over four years, with 25% of the underlying shares vesting on each anniversary of the grant date, subject to the employee being continuously employed by the company as of such vesting dates. The stock options vest over four years, with 25% of the shares underlying the option vesting on the first anniversary of the grant date and the remainder vesting with respect to 1/48th of the shares underlying the options on each monthly anniversary thereafter, subject to the employee being continuously employed by the company as of such vesting dates. The stock options have a ten-year term and an exercise price of $38.20 per share, equal to the per share closing price of Ultragenyx’s common stock on April 14, 2023.

On April 19, 2023 Targovax ASA (OSE: TRVX) reported its intention to rebrand the company as Circio to reflect its strategic shift to focus on accelerating development of its proprietary and innovative circular RNA (circRNA) platform (Press release, Targovax, APR 19, 2023, View Source [SID1234630315]). Subject to shareholder approvals at the Annual General Meeting to be held on 22 May 2023, Circio Holding ASA will assume the group’s listing on the Oslo stock exchange under the ticker CRNA.

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"The name Circio reflects our ambition to become a leader in circRNA, as well as the company´s heritage in immuno-oncology. CircRNA’s promise is demonstrated by an increasing number of circRNA financings, which accounted for more than 40% of private RNA biotech deal value globally in 2021-22, and by major strategic agreements by big pharma and biotech. With the rebranding to Circio, we are aiming to take a clear position in the emerging circRNA field and maximize our visibility and attractiveness to the global pharmaceutical industry and specialist international investors," Damian Marron, Chairman, said.

"circRNA offers important functional advantages over mRNA. Based on extensive experience, our leading circRNA scientists have invented a clearly differentiated vector system to generate circRNA in target tissues. Using this strategy, we can turn host cells into circRNA factories, thus providing an expanded toolbox of therapeutic options compared to current circRNA and mRNA approaches. In less than 15 months, we have established robust technical proof-of-concept for our approach, and key patent applications have been filed. Therefore, now is the right time to clearly signal our evolution into a circRNA-focused company" Dr. Erik Digman Wiklund, CEO, commented.

CircRNA is a naturally occurring class of RNA first reported in 2011 by two current Circio employees: VP & Head of Research Dr. Thomas B Hansen and CEO Dr. Erik D Wiklund. Due to their chemical structure, circRNAs are resistant to the main cellular RNA degradation mechanisms, which dramatically prolongs their half-life compared to linear mRNA. This feature can enable increased and more durable protein expression, as well as novel regulatory functionalities. Circio has an ambitious R&D strategy to engineer novel circRNA medicines for cancer, vaccines, and genetic disorders. The circRNA R&D activities are being conducted in the wholly owned subsidiary Circio AB based at the Karolinska Institute in Stockholm, Sweden.

Circio’s proprietary circVec platform is a modular genetic cassette delivering instructions for generation of multifunctional circRNAs. The most advanced therapeutic concept, circAde, builds on the company´s experience in oncolytic viruses to use engineered adenoviruses for delivery of circRNA to cancer cells. The circVec and circAde technology is protected by deep know-how and a rapidly expanding IP portfolio.

Circio remains committed to the ONCOS and TG programs. The KRAS immunotherapy TG01 is currently being tested in two clinical trials in pancreatic cancer and multiple myeloma through collaborative networks in the USA and Norway. A phase 2 study design combining ONCOS-102 with next generation checkpoint inhibitors in treatment resistant melanoma has been approved by the US FDA, and will, as previously communicated, be initiated once additional funding or a partner has been secured.

The renaming of Targovax ASA to Circio Holding ASA will be subject to shareholder approval at the annual general meeting (AGM) to be held on 22 May 2023 and formally enacted following such approval.