Entry into a material definitive agreement

On September 28, 2023, AIM ImmunoTech Inc. (the "Company") executed an Amended and Restated Material Transfer and Research Agreement (the "Agreement") with Roswell Park Cancer Institute Corporation d/b/a Roswell Park Comprehensive Cancer Center ("Roswell") that amends and restates the prior related agreements (Filing, 8-K, AIM ImmunoTech, SEP 28, 2023, View Source [SID1234635536]). Pursuant to the Agreement, Roswell will undertake ongoing and new Research Projects as set forth in Exhibit A to the Agreement related to utilizing the Company’s Ampligen and related technology (the "Research Project"). The Company will provide the Ampligen needed to conduct the Research Projects. The Agreement contemplates that the Research Projects may also be funded by various entities independent of AIM, such as the National Institutes of Health, foundations, Department of Defense, or University support. The Agreement will terminate on the later of completion of the Research Project, the written agreement of the parties or three years after the effective date of the Agreement. The foregoing summary of the Agreements does not purport to be complete and is qualified in its entirety by reference to the full text of the Agreement, which is attached as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference.

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Valerio Therapeutics Reports its Half-Year 2023 Financial Results and Provides an Update on its Activities

On September 28, 2023 Valerio Therapeutics S.A. (Euronext Growth Paris: ALVIO), hereafter "Valerio Therapeutics" or the "Company", a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR), reported its consolidated half-year financial results to June 30, 2023, and provides an update on its activities (Press release, Valerio Therapeutics, SEP 28, 2023, View Source [SID1234635523]).

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Dr. Shefali Agarwal, President and CEO of Valerio Therapeutics, said: "The first half of 2023 was an important phase for our Company. By renaming ourselves Valerio Therapeutics, we highlighted our will to use innovative technologies such as DNA decoys to advance new anti-cancer treatments.

AsiDNATM, our first-in-class drug candidate, is currently being evaluated in an ongoing 1b/2 trial in the United State. This study is in combination with Olaparib in recurrent ovarian, breast and metastatic castration-resistant prostate cancer and the objective is to assess the safety and tolerability of the combination as well as to determine the recommended Phase 2 dose. Patient recruitment is progressing, and Top-line results are expected this year.

In parallel, AsiDNATM has also continued to be evaluated in two additional studies in collaboration with French academic research centers, the first one by Gustave Roussy to combat PARP inhibitor resistance in second-line maintenance treatment of recurrent ovarian cancer, and the second one by the Institut Curie in combination with radiotherapy in recurrent high-grade glioma in children.

Finally, our R&D efforts have been focused on the optimization of our PlatONTM platform and the development new therapeutic agents in oncology and other therapeutic agents. We now have a lead candidate from the OX400 compound family, VIO-01 (formerly OX425), a pan DNA repair decoy. This product works by abrogating several DNA repair pathways, inducing a drug-driven synthetic lethality without the need of a combined treatment. This potentially is first of its kind product with a broad applicability and thus represents a promising drug candidate to move forward to clinical development. We continue to explore new therapeutic pathways with PlatONTM and think that PROTACs (PROteolysis-TArgeting Chimeras) technology and other tumor specific targeting options may be a novel class presenting several potential benefits when combined with our DNA decoy molecules.

By all these progresses, Valerio Therapeutics is well positioned to rapidly advance breakthrough therapeutic candidates through Phase 2 development and, eventually, to contribute to the treatment of cancer patients globally. Additionally, we are also continuing active evaluation of business partnerships that can be synergistic to our pipeline and the team."

FINANCIAL RESULTS FOR THE FIRST HALF OF 2023

Consolidated income statement (IFRS)

In thousands of euros

June 30, 2023

June 30,2022

Revenues, of which:

0

0

Recurring revenues

0

0

Non-recurring revenues

0

0

Operating expenses, including:

(11,622)

(9,631)

R&D expenditure with third parties

(5,643)

(4,107)

Other current operating income

28

282

Current operating income

(11,594)

(9,348)

Other non-recurring operating income

0

385

Income from companies accounted for by the equity method

Operating income after share of profit of associates

(11,593)

(8,963)

Financial income

(50)

(2,448)

Income tax expense

0

(59)

Net income

(11,644)

(11,471)

The half-year accounts as of June 30, 2023, drawn up according to IFRS standards and approved by the Board of Directors on September 28, 2023, have not been audited nor been the subject of a limited review; being remembered that a new auditor was appointed at the shareholders’ meeting held on 6 June 2023.

The Group did not record any consolidated revenues for the period ended June 30, 2023.

Operating expenses amounted to €11.6 million. The increase compared to €9.6 million in 2022 is related to the strengthening of the scientific teams, and to the growth in R&D expenses. The latter increased by €1.5 million in the first half of 2023 to reach €5.6 million, mainly due to industrial development and manufacturing of clinical batches for AsiDNATM.

The financial loss as of June 30, 2023, amounted to €50k compared to a loss of €2.4 million as of June 30, 2022, mainly due to the cost of the bond issue with SWK Holdings.

The Group’s total net loss was thus €11.6 million in the first half of 2023, compared with a loss of €11.4 million for the same period in 2022.

CASH POSITION AS OF JUNE 30, 2023

As of June 30, 2023, the Group’s cash position was €16.8 million, compared to €14.6 million as of December 31, 2022. This increase comes from a €12 million financing obtained on June 9, 2023, from the Company’s historical shareholders, Invus and Financière de la Montagne and a new investor, Agenus Inc. The net proceeds of this reserved share issue are intended for the development of VIO-01 (formerly OX425), both clinically and industrially, for ongoing and future clinical trials and more generally, to finance the Company’s current expenses.

Following the completion of the capital increase, Invus Public Equities LP and Financière de la Montagne held 28.5% and 19% of the Company’s capital respectively, based on a total of 154,364,273 shares. Agenus held 11.5% of the Company’s capital.

These resources provide the Company with sufficient visibility to carry out its projects, including the expansion of the clinical development of AsiDNATM and the continuation of the preclinical development of the platONTM compounds, including VIO-01, until the second quarter of 2024.

HIGHLIGHTS OF THE FIRST HALF OF 2023 AND RECENT DEVELOPMENTS

AsiDNATM

In the United States, the multi-center Phase 1b/2 study evaluating the safety and efficacy of AsiDNATM in combination with the PARP inhibitor Olaparib in patients with epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed despite initial treatment with PARP inhibitors was initiated in December 2022, and is currently ongoing, with 1 patient enrolled in the study. The plan is to continue enrollment in the dose escalation phase until the third quarter 2023, convene a Safety Monitoring Committee (SMC) to review the data and identify dose for expansion.

In addition, during the first half of the year 2023, Valerio Therapeutics continued supporting two investigator induced studies conducted in collaboration with two academic research centers of excellence in oncology:

– The Revocan phase 1b/2 trial evaluating the addition of AsiDNA to combat PARP inhibitor resistance in second-line maintenance treatment of recurrent ovarian cancer. Gustave Roussy is the promoter of this study. The pace of recruitment has been slower than expected and 15 patients have been enrolled in this first part of the study. The first interim analysis of 10 patients was conducted in the first half of 2023, showing a Disease Control Rate (DCR) of 70 %, an overall reduction in the percentage of CA125 (tumor marker) in responding patients, which serves as a proof of concept of the treatment with AsiDNATM.

– The Phase 1b/2 trial evaluating AsiDNATM in combination with radiotherapy in recurrent high-grade glioma in children, an indication with a particularly poor prognosis. The Institut Curie is the sponsor of this study, which is supported by a grant from the European Fight Kids Cancer program. The Company has announced the treatment of a first patient in August 2022, 7 patients were enrolled in this first part of the study, no data from the study has been disclosed yet.

VIO-01 (formerly OX425)

During the first half of 2023, the Company continued to optimize the OX400 pan-DDR DNA decoy family to improve its action on repair proteins, involved in the tumor DNA repair cascade, and its activation of the antitumor immune response via the cGAS-STING pathway.

VIO-01, formerly OX425, is a Pan-DDR DNA Decoy Targeting Multiple Proteins & Repair Pathways and represents the most optimal drug candidate selected to enter preclinical development. VIO-01 traps several DDR Proteins Inhibiting Different DNA Repair Pathways. VIO-01 reaches the nucleus and acts as a decoy for several DNA repair enzymes. It has an increased resistance to nucleases and plasmatic stability.

Valerio Therapeutics presented new preclinical data confirming the pan-DDR DNA decoy effect of VIO-01 and the high anti-tumor activity in tumor models independently from the homologous recombination repair status on April 19, 2023, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Also, the Company presented new preclinical data confirming VIO-01’s capability to abrogate several DNA repair pathways and induce a drug-driven synthetic lethality, without the need of a combined treatment.

3rd generation of PlatONTM platform

Valerio Therapeutics continued to optimize the PlatON platform to develop more potent assets coupled to innovative technologies, with the objective to combine PlaTON platform’s DNA decoys with the targeted protein degradation strategy offered by PROTACs (PROteolysis-TArgeting Chimeras) technology. PROTACs technology and other tumor specific targeting options may be a novel class of heterobifunctional molecules that can selectively degrade target proteins within cells. This approach offers several advantages over the other molecules involved in modulating the DNA damage response, such as increased selectivity and reduced toxicity. This specific strategy involves generating DecoyTAC combining our vectorized DNA decoy molecules capable of efficient cell penetration with a linker+E3 ligand promoting the complete degradation of the target proteins, thereby presenting a novel mechanism of action.

The exploration of the convergence of PROTACs and DNA Decoys aims to not only propose new therapeutic modalities against DDR proteins but also against transcription factor proteins that are challenging to target. Through these efforts, the Company strive to advance the field of oncology drug development and contribute to the treatment of cancer patients.

Governance and Corporate

The Annual General Meeting of June 6, 2023, renewed the terms of Financière de la Montagne, represented by Mr. Nicolas Trebouta, and Robert Coleman as directors for three years. As of the date of this report, the Board of Directors is composed of 7 members, 6 men and 1 woman, including 3 independent members.

The Annual General Meeting also approved the change of company name to Valerio Therapeutics. This name change was accompanied by a new identity designed to better represent Valerio Therapeutics’ ability to rapidly advance breakthrough therapeutic candidates through Phase 2 development, and to collaborate with partners for further development and commercialization. The ISIN code remained unchanged.

OUTLOOK

In 2023, the Company will continue to pursue its value creation strategy based on the development of its therapeutic innovations up to proof-of-concept studies in humans, and then generate revenues through agreements with other pharmaceutical companies capable of pursuing their development.

AsiDNA

Enrollment to continue in the U.S. phase 1b/2 trial in combination with Olaparib in ovarian, breast and prostate cancers to identify the RP2D in combination with Olaparib.

Clinical updates expected in the second half of 2023 from phase 1b/2 trials conducted in France and European Union under the sponsorship of academic centers:

REVOCAN trial with Gustave Roussy;
Pediatric trial in High-Grade Glioma with Institut Curie;
Submissions for publications in international scientific journals of the results of preclinical or clinical studies as part of the development plan to demonstrate the potential of AsiDNA.
VIO-01 (formerly OX425)

Finalization of the IND-enabling preclinical studies.
Preparation of an IND application with the FDA in second half-year 2023.
platON

Continued evaluation and optimization of PlatONTM platform and potential new drug candidates.
The 2023 half-year financial report is available on the Company’s website.

Gamida Cell to Present at Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting

On September 28, 2023 Gamida Cell Ltd. (Nasdaq: GMDA), a cell therapy pioneer working to turn cells into powerful therapeutics, reported that it will be presenting at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting (SITC 2023) taking place in San Diego, CA and virtually November 1-5, 2023 (Press release, Gamida Cell, SEP 28, 2023, View Source [SID1234635522]).

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Details about the poster presentations are as follows:

Title: GDA-201, nicotinamide (NAM) expanded NK cells derived from peripheral apheresis, show unique culture kinetics and increased expansion
Abstract number: 401
Presenter: Avner Yeffet, Ph.D.
Time: Friday, November 3, 2023, 9:00 a.m. – 7:00 p.m. PDT
Location: Exhibit Halls A and B1

Title: Significant myeloid and dendritic cellular enrichment of omidubicel graft suggests fast homeostatic proliferation of lymphoid populations
Abstract number: 336
Presenter: Dima Yackoubov
Time: Saturday, November 4, 2023, 9:00 a.m. – 8:30 p.m. PDT
Location: Exhibit Halls A and B1

About GDA-201
GDA-201 is an intrinsic NK cell therapy candidate being investigated for the treatment of hematologic malignancies. A multicenter Phase 1 study of GDA-201 for the treatment of non-Hodgkin lymphoma is ongoing (NCT05296525). Results are expected in Q1 2024.

GDA-201 is an investigational cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority.

Omisirge (omidubicel-onlv) Indication

Omisirge is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from cord blood indicated for use in adults and pediatric patients 12 years and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection.

Important Safety Information for Omisirge

BOXED WARNING: INFUSION REACTIONS, GRAFT VERSUS HOST DISEASE, ENGRAFTMENT SYNDROME, AND GRAFT FAILURE

Infusion reactions may be fatal. Monitor patients during infusion and discontinue for severe reactions. Use is contraindicated in patients with known allergy to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin or bovine material.
Graft-versus-Host Disease may be fatal. Administration of immunosuppressive therapy may decrease the risk of GvHD.
Engraftment syndrome may be fatal. Treat engraftment syndrome promptly with corticosteroids.
Graft failure may be fatal. Monitor patients for laboratory evidence of hematopoietic recovery.
Contraindications

OMISIRGE is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin, or bovine products.

Warnings and Precautions

Hypersensitivity Reactions
Allergic reactions may occur with the infusion of OMISIRGE. Reactions include bronchospasm, wheezing, angioedema, pruritis and hives. Serious hypersensitivity reactions, including anaphylaxis, may be due to DMSO, residual gentamicin, Dextran 40, human serum albumin (HSA) and bovine material in OMISIRGE. OMISIRGE may contain residual antibiotics if the cord blood donor was exposed to antibiotics in utero. Patients with a history of allergic reactions to antibiotics should be monitored for allergic reactions following OMISIRGE administration.

Infusion Reactions
Infusion reactions occurred following OMISIRGE infusion, including hypertension, mucosal inflammation, dysphagia, dyspnea, vomiting, and gastrointestinal toxicity. Premedication with antipyretics, histamine antagonists, and corticosteroids may reduce the incidence and intensity of infusion reactions. In patients transplanted with OMISIRGE in clinical trials, 47% (55/117) patients had an infusion reaction of any severity. Grade 3-4 infusion reactions were reported in 15% (18/117) patients. Infusion reactions may begin within minutes of the start of infusion of OMISIRGE, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of infusion reactions during and after OMISIRGE administration. When a reaction occurs, pause the infusion and institute supportive care as needed.

Graft-versus-Host Disease
Acute and chronic GvHD, including life-threatening and fatal cases, occurred following treatment with OMISIRGE. In patients transplanted with OMISIRGE Grade II-IV acute GvHD was reported in 58% (68/117). Grade III-IV acute GvHD was reported in 17% (20/117). Chronic GvHD occurred in 35% (41/117) of patients. Acute GvHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Patients treated with OMISIRGE should receive immunosuppressive drugs to decrease the risk of GvHD, be monitored for signs and symptoms of GvHD, and treated if GvHD develops.

Engraftment Syndrome
Engraftment syndrome may occur because OMISIRGE is derived from umbilical cord blood. Monitor patients for unexplained fever, rash, hypoxemia, weight gain, and pulmonary infiltrates in the peri-engraftment period. Treat with corticosteroids as soon as engraftment syndrome is recognized to ameliorate symptoms. If untreated, engraftment syndrome may progress to multiorgan failure and death.

Graft Failure
Primary graft failure occurred in 3% (4/117) of patients in OMISIRGE clinical trials. Primary graft failure, which may be fatal, is defined as failure to achieve an absolute neutrophil count greater than 500 per microliter blood by Day 42 after transplantation. Immunologic rejection is the primary cause of graft failure. Monitor patients for laboratory evidence of hematopoietic recovery.

Malignancies of Donor Origin
Two patients treated with OMISIRGE developed post-transplant lymphoproliferative disorder (PTLD) in the second-year post-transplant. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. The etiology is thought to be donor lymphoid cells transformed by Epstein-Barr virus (EBV). Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias. One patient treated with OMISIRGE developed a donor-cell derived myelodysplastic syndrome (MDS) during the fourth-year post-transplant. The natural history is presumed to be the same as that for de novo MDS. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Gamida Cell at (844) 477-7478.

Transmission of Serious Infections
Transmission of infectious disease may occur because OMISIRGE is derived from umbilical cord blood. Disease may be caused by known or unknown infectious agents. Donors are screened for increased risk of infection, clinical evidence of sepsis, and communicable disease risks associated with xenotransplantation. Maternal and infant donor blood is tested for evidence of donor infection. See full Prescribing Information, Warnings and Precautions, Transmission of Serious Infections for list of testing performed. OMISIRGE is tested for sterility, endotoxin, and mycoplasma. There may be an effect on the reliability of the sterility test results if the cord blood donor was exposed to antibiotics in utero. Product manufacturing includes bovine-derived reagents. All animal-derived reagents are tested for animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other transmissible infectious diseases and disease agents. Test results may be found on the container label and/or in accompanying records. If final sterility results are not available at the time of use, Quality Assurance will communicate any positive results from sterility testing to the physician. Report the occurrence of transmitted infection to Gamida Cell at (844) 477-7478.

Transmission of Rare Genetic Diseases
OMISIRGE may transmit rare genetic diseases involving the hematopoietic system because it is derived from umbilical cord blood. Cord blood donors have been screened to exclude donors with sickle cell anemia, and anemias due to abnormalities in hemoglobins C, D, and E. Because of the age of the donor at the time cord blood collection takes place, the ability to exclude rare genetic diseases is severely limited.

ADVERSE REACTIONS

The most common adverse reactions (incidence > 20%) are infections, GvHD, and infusion reaction.

Please see full Prescribing Information, including Boxed Warning.

First Patient Dosed in Phase 1b Clinical Trial of Synthekine’s α/β Biased IL-2, STK-012, for Treatment of Solid Tumors

On September 28, 2023 Synthekine Inc., a leader in engineered cytokine therapeutics, reported that the company has completed phase 1a dose escalation and dosed the first patient in the Phase 1b portion of a clinical trial evaluating its α/β biased IL-2, STK-012, for the treatment of solid tumors (Press release, Synthekine, SEP 28, 2023, View Source [SID1234635521]).

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STK-012 is engineered to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as NK cells, which are associated with IL-2 toxicity. Synthekine recently completed the Phase 1a dose-escalation portion of the study in patients with various advanced solid tumors, with results suggesting a differentiated safety profile and monotherapy efficacy. The Phase 1b portion of the study will include dose expansion cohorts to evaluate STK-012 as monotherapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types, including renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC).

"IL-2 is critical for T cell activation and promoting antitumor immunity," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "However, to date, no one has been able to unravel the pleiotropic nature of IL-2 and develop a drug that truly expands therapeutic index. STK-012 is built from unique insights into IL-2 biology and is the first α/β biased IL-2 with clinical results. We have observed encouraging single-agent activity with STK-012 in dose escalation and are excited to begin our cohort expansion studies."

"High-dose (HD) IL-2 has brought durable benefits to patients, even remissions for patients with metastatic melanoma and kidney cancer. But its significant toxicity and limited efficacy have prevented HD IL-2 from fulfilling its transformative potential in devastating cancers like non-small cell lung cancer," said David McDermott, M.D., a study investigator and Chief of Medical Oncology at Beth Israel Deaconess Medical Center, and Professor of Medicine at Harvard Medical School. "STK-012 represents a promising new approach in the field of cancer immunotherapy, offering a highly selective strategy for targeting IL-2 pathways that could potentially transform the treatment paradigm for these and other solid tumor indications."

The Phase 1b dose expansion portion of the clinical trial is an open-label, nonrandomized multi-center study currently enrolling patients. In addition to assessing the anti-tumor activity of STK-012 monotherapy, this study will continue to evaluate safety, tolerability and pharmacokinetics. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

Results from the Phase 1a portion of the study will be presented at a future medical meeting.

Oncoinvent To Present Initial Safety Data from the Phase 1 Trial of Radspherin® in Ovarian Cancer Patients at the 24th Congress of the European Society of Gynaecological Oncology (ESGO)

On September 15, 2023 Oncoinvent AS, a clinical stage company advancing alpha emitter therapy across a variety of solid cancers, reported the presentation of initial safety data from the ongoing Phase 1 clinical trial evaluating the recommended dose, safety and tolerability of Radspherin in patients with recurrent ovarian cancer at the 24th Congress of the European Society of Gynaecological Oncology (ESGO) being held at the Istanbul Congress Center in Istanbul, Türkiye from September 28 – October 1, 2023 (Press release, Oncoinvent, SEP 28, 2023, View Source [SID1234635520]). The presentation, titled "First Experience With Intra-Abdominal 224Radium-Labelled Microparticles (Radspherin) After Cytoreductive Surgery For Peritoneal Metastasis In Recurrent Epithelial Ovarian Cancer (Phase 1 Study)" will be presented on September 30, 2023 from 9:24 a.m. to 9:32 a.m. local time (5:24 a.m. ET).

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"Oncoinvent is proud to present safety data from our lead candidate, Radspherin at a major congress of the global gynecological cancer community. We believe this is an important first step as we advance the development of Radspherin as a new treatment for patients with advanced ovarian cancer," says CEO Anders Månsson.

Details of the presentation are as follows:

Session: MO3 Mini Oral Session – Ovarian Cancer
Presentation Title: First Experience With Intra-Abdominal 224Radium-Labelled Microparticles (Radspherin) After Cytoreductive Surgery For Peritoneal Metastasis In Recurrent Epithelial Ovarian Cancer (Phase 1 Study)
Presentation Board Number: 850
Presenting Author: Els Van Nieuwenhuysen, MD
Presentation Date and Time: September 30th, 2023, from 9:24 a.m. to 9:32 a.m. local time (5:24 a.m. ET)

The ongoing Phase 1 study is designed to evaluate the recommended dose, safety and tolerability of Radspherin injected intraperitoneally following secondary cytoreductive surgery. The safety interim analysis after completion of the dose-limiting toxicity (DLT) period demonstrated that Radspherin was well tolerated. The highest dose of 7 MBq was recommended following the completion of dose escalation of 1-2-4-7 MBq, as no DLT was observed.