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.

On April 19, 2023, Soligenix, Inc. (the "Company") and its subsidiaries, Soligenix UK Limited, Enteron Pharmaceuticals, Inc., Soligenix BioPharma Canada Incorporated, Soligenix NE B.V., and Soligenix Biopharma HI, Inc., as borrowers (collectively referred to as the "Borrower"), entered into an amendment (the "Amendment") to the Loan and Security Agreement (the "Loan Agreement") dated December 15, 2020 with Pontifax Medison Finance (Israel) L.P. and Pontifax Medison Finance (Cayman) L.P. (collectively, the "Lenders") and Pontifax Medison Finance GP, L.P., in its capacity as administrative agent and collateral agent for itself and Lenders (Filing, 8-K, Soligenix, APR 19, 2023, View Source [SID1234630314]).

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The Amendment eliminates any prepayment premium allowing the Borrowers to prepay the outstanding principal amount at any time, plus accrued and unpaid interest, without incurring a prepayment fee, which under the Loan Agreement was 1% of the outstanding principal. The Amendment also provides that, if the Company raises $5.6 million in gross proceeds by December 31, 2023, the interest-only payment-period end-date will be extended to December 31, 2023, which under the Loan Agreement was January 1, 2023. The minimum cash covenant, which requires the Borrowers to maintain at all times a certain qualified cash balance and was previously set at $4.5 million, was reduced by the Amendment to $1.5 million. The Amendment also provides that, if the Company raises $10 million in gross proceeds by December 31, 2023, the interest-only period would be extended to June 30, 2024 and the minimum cash balance requirement would be reduced to $0.

As consideration for the Amendment, the Company (a) repaid $5.0 million of the outstanding principal (without incurring a prepayment premium), reducing the remaining outstanding principal amount to $3.0 million, and (b) reduced the conversion price with respect to the remaining principal amount under the Loan Agreement to (i) 90% of the closing price of the Company’s common stock on the day before the delivery of the conversion notice with respect to the first 588,599 shares of the Company’s common stock issuable upon conversion and (i) $1.70 with respect to all shares of the Company’s common stock issuable upon conversion in excess of the first 588,599 shares so issued.

None of the other terms of the Loan Agreement were modified in any material respect.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the Amendment, which is attached hereto as Exhibit 10.1 and incorporated herein by reference.

On April 19, 2023 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, reported data from four presentations at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Sana Biotechnology, APR 19, 2023, View Source [SID1234630313]).

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"Sana remains focused on improving outcomes, predictability, and access with cell and gene therapies, and we have several programs looking to expand on the transformative potential for CAR T cells in treating hematological cancers," said Terry Fry, Sana’s Senior Vice President and Head of T Cell Therapeutics. "At AACR (Free AACR Whitepaper), we presented data highlighting the potential of our hypoimmune platform to "hide" allogeneic CAR T cells from immune recognition, improving CAR T cell persistence and anti-tumor effect. Other data highlighted the progress and potential of SG299, the first drug candidate from our fusogen platform, in generating CD19-directed CAR T cells with in vivo delivery. In 2023, we look forward to initial clinical data for SC291, allogeneic CAR T cells for patients with B cell cancers; filing an IND for SC262, allogeneic CAR T cells for patients that have failed previous CAR T therapy; and filing an IND for SG299, our in vivo CAR delivery program for patients with B cell cancers."

The poster (abstract 4091) titled "Engineered hypoimmune CAR T cells provide lasting tumor control in immunocompetent allogeneic humanized mice even with re-challenge" described preclinical data on hypoimmune (HIP)-modified allogeneic CD19 directed CAR T cells. The study results showed that HIP CD19-directed CAR T cells were functionally immune evasive in allogeneic humanized mouse models. The cells persisted and remained functional over multiple months in an allogeneic immune system, even with tumor re-challenge after 90 days. In contrast, although CD19-directed CAR T cells lacking hypoimmune edits showed an initial tumor response, they were eliminated by the allogeneic immune system and tumor recurred after 30 days in the majority of animals.

The late-breaking poster (abstract LB311) titled "Increased potency of CD8-targeted fusosomes enhances CAR gene delivery to resting primary T cells" described the preclinical efficacy of a CD8-targeted fusosome encoding a CD19 CAR transgene manufactured using an improved process. The improved process generates fusosomes with increased potency that result in increased in vivo CAR T generation and increased tumor control. CD8-targeted fusosomes were also evaluated in a clinically relevant mock extracorporeal delivery setting, which potently generated CD19-directed CAR T cells. A CD8-targeted fusosome delivering a CD19 CAR transgene has the potential to provide an off-the-shelf therapeutic approach to generate CD19-directed CAR T cells in vivo and without lymphodepleting chemotherapy.

The poster (abstract 2735) titled "Development of a novel, fully human anti-CD19 chimeric antigen receptor for in vivo delivery via CD8-targeted fusosomes" compares preclinical data on a fully human CD19-directed CAR, which comprises a human CD19 binder developed at Sana, to a standard murine FMC63 CAR. CD19-directed CAR T cells with the fully human CD19 CAR demonstrated comparable efficacy to CD19-directed CAR T cells with an FMC63 CAR in both in vitro and in vivo models. CD8-targeted fusosomes delivering this fully human CD19 CAR into T cells demonstrated anti-tumor efficacy in vivo. The use of a fully human CD19 binder has the potential to reduce the immunogenicity of the CD19 CAR relative to an FMC63 CAR and has potential applicability in both Sana’s hypoimmune CAR T cell platform and in vivo CAR T cell platform.

The poster (abstract 2734) titled "Modulation of resting T cell status to enhance transduction and CAR T expansion following exposure to CD8-targeted fusosomes" highlighted the preclinical efficacy of treatments to modulate resting T cell status to enhance transduction and generation of CAR T cells by a with CD8-targeted fusosomes encoding a CD19 CAR transgene, both prior to and after delivery of such fusosomes. Although CD8-targeted fusosomes alone were effective at transducing resting T cells, pre-treatment of resting T cells with IL-7 increased transduction efficiency in vitro and also increased anti-tumor efficacy in vivo. Adding rapamycin to IL-7 in the pre-treatment setting further increased the fusosomes’ transduction efficiency. When IL-7 was delivered post-transduction, there was CAR T cell expansion, resulting in improved in vitro cytotoxicity. When given systemically, IL-7 supported the expansion of in vivo fusosome-generated CAR T cells and increased anti-tumor efficacy compared to fusosome only. Combinations of CD8-targeted fusosomes with cytokine treatments could be implemented to further increase transduction and CAR T cell generation, drive CAR T cell expansion, and improve patient outcomes.

About Sana’s Hypoimmune Platform
Sana’s hypoimmune platform is designed to create cells ex vivo that can "hide" from the patient’s immune system to enable the transplant of allogeneic cells without the need for immunosuppression. We are applying hypoimmune technology to both donor-derived allogeneic T cells, with the goal of making potent and persistent CAR T cells at scale, and pluripotent stem cells, which can then be differentiated into multiple cell types at scale. Preclinical data from a variety of cell types demonstrate that these transplanted allogeneic cells can evade both the innate and adaptive arms of the immune system while retaining their function. Our most advanced programs using hypoimmune technology include our allogeneic CAR T program targeting CD19+ cancers (SC291), our allogeneic CAR T program targeting CD22+ cancers (SC262), our allogeneic CAR T program targeting BCMA+ cancers (SC255), and our stem-cell derived pancreatic islet cell program for patients with type 1 diabetes (SC451).

About Sana’s Fusogen Platform
Sana’s fusogen platform is designed to optimize in vivo cell specific delivery of genetic material. Our goal is to be able to repair and control genes in cells. Engineering cells in vivo requires the development of both an appropriate delivery vehicle, as well as an active component to effectively modify the target cell. Fusogens are naturally occurring cell-targeting proteins. Sana reengineers these proteins to target specific cell surface receptors, enabling cell-specific delivery to many different types of cells. The platform was developed to deliver an active component to any cell in a specific, predictable, and repeatable way. This technology is the backbone of Sana’s in vivo delivery platform and is incorporated into various product candidates, including SG299, a CD8-targeted fusosome that delivers a CD19 CAR to target CD19+ cancer cells.