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.

On April 19, 2023 Purple Biotech Ltd. ("Purple Biotech", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies that harness the power of the tumor microenvironment (TME) to overcome tumor immune evasion and drug resistance, reported new results presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando (Press release, Purple Biotech, APR 19, 2023, View Source [SID1234630312]). The results demonstrate the potential of NT219, the Company’s novel small molecule dual inhibitor of IRS1/2 and STAT3 escape mechanisms, to work synergistically with either anti-PD1 or anti-CTLA4 drugs to reprogram the immune profile in the TME and convert resistant tumors to responders to Immune Checkpoint Blockage (ICB) therapies. The study was led by researchers at The University of Texas MD Anderson Cancer Center. Main results are as follows:

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NT219 induced significant PDL1 expression in melanoma cells in-vitro and showed a synergistic effect with anti-PD1 therapy in tumor growth inhibition in-vivo. The induction of PDL1 by NT219 was much higher in the ICB-resistant melanoma strain as compared to ICB-sensitive cells, suggesting the potential to re-sensitize refractory tumors to anti-PD1 therapy.

Treatment of immunocompetent mice bearing ICB-resistant tumors with NT219 in combination with either anti-PD1 or anti-CTLA4 therapies showed a significant increase in activated CD8 cytotoxic T cells and NK cells in the TME; this effect was seen in parallel with a significant decrease in the infiltration of immunosuppressive populations, including regulatory T cells, and myeloid-derived suppressor cells, and M2 macrophages. No such effects were detected with either therapy alone.

Similarly, NT219 in combination with anti-PD1 showed synergistic effects inducing significant tumor growth inhibition of ICB-resistant tumors, while each therapy alone had no effect.

The ICB-resistant clone showed higher levels of both IRS1 and STAT3 activation in comparison with the ICB-sensitive clone of the same origin melanoma cells. Treatment with NT219 diminished both IRS1 and STAT3 phosphorylation in both cloned cell lines and showed a durable effect on these target proteins, which are known to be involved in drug resistance.

"These results suggest that combining ICB with NT219 may be a promising strategy to reprogram the immune profile of the TME to enhance anti-tumor immunity, turning ‘cold’ tumors ‘hot’ and re-sensitizing resistant tumors to anti-PD1 therapy", said Hadas Reuveni, PhD, VP R&D at Purple Biotech. "The insidious process by which tumors become resistant to so many of our most promising cancer drugs robs patients of hope and of time with their families. Lengthening the duration of treatment as well as broadening the patient population that may benefit from these treatments address the highest obstacles of ICB therapies today."

Results from 5073/7 "NT219 induces tumor PD-L1 expression and potentiates anti-PD-1 efficacy" presented as a poster on April 18, 2023, at the AACR (Free AACR Whitepaper) 2023 Annual Meeting.

The full poster can be viewed on the Purple Biotech Website at View Source

About NT219

NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. In a Phase 1/2 study of NT219, the Company is currently advancing it as a monotherapy treatment of solid tumors, and in a dose escalation in combination with cetuximab for the treatment of recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) or colorectal adenocarcinoma (CRC). These studies will be followed by an expansion phase of NT219 at its recommended Phase 2 level in combination with cetuximab in patients with recurrent and metastatic SCCHN.

On April 19, 2023 Onchilles Pharma, a private biotech company developing novel cancer therapeutics that leverage myeloid biology, reported new preclinical data on N17350, a first-in-class biologic therapeutic inspired by ELANE, a protein found in neutrophils that is part of a newly discovered innate cancer-killing pathway (Press release, Onchilles Pharma, APR 19, 2023, View Source [SID1234630310]). The data demonstrate N17350, as a monotherapy or in combination with checkpoint inhibitors, abrogates tumor growth, induces a robust immune signature with the potential to establish durable remission, and demonstrates no acquired resistance. These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 taking place in Orlando.

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"While significant therapeutic innovation has occurred in immuno-oncology, it’s clear that we need to continue to explore new treatment paradigms that can selectively kill tumors and yield durable therapeutic responses. When we discovered the ELANE pathway, we saw the potential for a novel approach in immuno-oncology that combines broad activity in cancer cells but not in normal cells, robust immune system activation with immunological memory, and an inability to develop resistance," said Lev Becker, Ph.D., Scientific Founder and Board Member of Onchilles Pharma. "N17350 was specifically designed to mobilize the ELANE-mediated cancer-killing pathway, and in addition to its potent single agent activity, we believe it could enhance most immunotherapies, lead to global responses, and represent a new treatment modality in immuno-oncology."

Data presented at AACR (Free AACR Whitepaper) show that in the CT26 tumor model, a single dose of N17350 abrogated tumor growth, maintained tumor-free status upon 90-day rechallenge with no observed toxicity, and enhanced survival compared to standard of care chemotherapy. Also presented were data from the 4T1 tumor model, where a single dose of N17350 demonstrated tumor regression and an abscopal effect driven by CD8+ T cells to control lung metastases. Furthermore, in the 4T1 model, N17350 in combination with anti-CTLA4 antibody treatment, demonstrated the potential to enable immune checkpoint inhibitor efficacy in an immunologically "cold" tumor model.

"We have generated a substantial amount of preclinical data demonstrating N17350 is unlike any other immuno-oncology therapeutic approach," Court R. Turner J.D., Co-Founder & Executive Chair of Onchilles Pharma. "These data compel us to move N17350 into the clinic to help patients with limited treatment options."

Click here to download the poster.

About N17350 and the ELANE Pathway

First described in research published in Cell from the lab of Onchilles’ Co-Founder Lev Becker, human neutrophils release catalytically active neutrophil elastase, called ELANE, which initiates a complex killing mechanism that culminates in cancer cell apoptosis at the initial tumor site as well as increases adaptive immunity that attacks distant metastases. ELANE selectively kills cancer cells by proteolytically liberating the CD95 death domain, which interacts with histone H1. This starts a complex cell death program only active in cancer cells that suppresses cell survival pathways, induces DNA damage, elevates mitochondrial reactive oxygen species production, and ultimately activates apoptosis effectors. The team at Onchilles translated the ground-breaking scientific discovery of ELANE, into a proprietary set of molecules including N17350, that mobilize the ELANE-mediated cancer-killing pathway and have the potential to treat a wide variety of tumor types with an optimal safety and efficacy profile.

On April 19, 2023 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage drug-development company focused on developing DNA-mediated immunotherapy and next-generation vaccines, reported that a poster highlighting the Company’s DNA-based immunotherapy IMNN-001 was presented on April 18 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando (Press release, IMUNON, APR 19, 2023, View Source [SID1234630309]). IMNN-001 (formerly GEN-1) is a DNA-based interleukin-12 (IL-12) immunotherapy currently in Phase 2 clinical development for the localized treatment of advanced ovarian cancer. The poster was presented by Jean Boyer, Ph.D., IMUNON’s vice president of preclinical research, and can be found on the company’s website.

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The poster is titled "Efficacy of IMNN-001, an Interleukin-12 Immune Gene Therapy, at Different Dose Frequencies." In the study, IMNN-001 dosing regimens were examined for efficacy in ID8 tumor-bearing mice either weekly, every two weeks or every three weeks. The control group of 15 mice were injected with 2.5 million cancer cells and remained untreated. Six animals from each group dosed were harvested for translational research (TR) after five weekly (three every two-week and two every three-week) treatments, respectively. The remaining four animals in each group were followed for weight change (tumor burden) and survival.

Additionally, TR evaluated change in ascites T cell populations. There was a gradual rise in tumor burden and mortality in all treatment groups with comparable rates between the once weekly and once every two weeks regimen. The once every three weeks regimen had a relatively higher mortality rate and higher tumor burden. There were similar or higher increases in T cells and B cells with reduced treatment frequency with lesser increases in myeloid cell density with reduced treatment frequency.

Researchers concluded that IMNN-001 demonstrated stimulation of the immune response in the ID8 ovarian tumor model. Of the three dosing regimens tested, the once every 2-week regimen demonstrated comparability to the weekly regimen while showing superiority to the once every 3-week regimen, particularly with respect to mortality and tumor burden. Thus, exploring once every 2-week dosing of IMNN-001 in human studies is warranted.

Commenting on the presentation, Dr. Corinne Le Goff, president and chief executive officer of IMUNON, said, "We are delighted that our work was selected for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, a very prestigious industry conference. This research in mice will underpin the dosing frequency being investigated in our upcoming Phase 1/2 combination study with IMNN-001 and bevacizumab following neoadjuvant chemotherapy in advanced ovarian cancer, along with any additional combination studies we may pursue in the future."