On September 29, 2023 Renovaro Biosciences Inc. (NASDAQ: RENB) (Renovaro), an advanced, preclinical biotechnology firm in cell, gene and immunotherapy reported to have signed a definitive agreement to combine with GEDi Cube Intl Ltd., (GEDi Cube) an AI medical technology company, in which GEDi Cube will become a wholly-owned subsidiary of Renovaro in a stock-for-stock acquisition (the "Transaction") (Filing, 8-K, Enochian BioSciences, SEP 29, 2023, View Source [SID1234635537]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

If completed, the Transaction will result in a combined company that will offer advanced early diagnosis and early identification of recurring cancer as well as potential therapies for several critical diseases such as pancreatic cancer and other solid tumors with poor life expectancy. It is expected that the combined company will have a unique advantage: Renovaro Biosciences’ pre-clinical and clinical trial data could be utilized to accelerate GEDi Cube’s AI capabilities that, in turn, could potentially help to accelerate Renovaro’s development of potential new therapies. AI will be used to advance the fields of diagnosis and treatment with the aim of redefining the future of medicine.

"We believe GEDi Cube’s AI technology will enhance and accelerate the development of treatments we are currently pursuing as well as power the discovery of new therapeutic approaches for cancer and other diseases," said Dr. Mark Dybul, CEO of Renovaro Biosciences. "The combined company will have independent operating divisions that will allow each technology to move as quickly as possible to commercialization while the collaboration between divisions will aim to drive new advances in both AI and medicine."

"I believe this is a unique opportunity to leverage the capabilities of our two companies, allowing us to accelerate our product development roadmap and our potential to improve diagnostics and treatments for many cancers," said Craig Rhodes, CEO of GEDi Cube. "We expect to begin offering commercial diagnostic products in 2024 that, in our view, will be comparable or superior to what is currently in the marketplace. We are looking forward to this exciting new venture."

GEDi Cube has been developing its innovative technologies over the last decade and has already validated early diagnosis of lung cancer in humans at a leading university hospital. The company has also validated technology to target 12 additional cancers, including pancreatic and breast cancer.

Renovaro Biosciences has developed advanced cell, gene and immunotherapy techniques designed to reignite the body’s natural tumor-fighting capabilities. The company expects to begin human Phase 1/2 clinical trials of its leading candidate for pancreatic cancer and other solid tumors with poor life expectancy by the second half of 2024.

About the Transaction

The Transaction is structured as a stock-for-stock acquisition whereby all of GEDi Cube’s outstanding equity interests will be exchanged for shares of Renovaro common stock. Following the closing of the Transaction, GEDi Cube equity holders are expected to own approximately 50% of the combined company, subject to certain adjustments provided for in the definitive agreement. The agreement was executed by a supermajority controlling interest of 78 percent of GEDi Cube shareholders; it is expected the remaining 22 percent will be included in the agreement prior to closing.

The boards of directors of both companies have unanimously approved the definitive agreement. The Transaction is expected to close late in the fourth quarter of 2023 or early 2024, subject to satisfying certain closing conditions, including the receipt of stockholder approval by Renovaro stockholders of the issuance of the shares of Renovaro common stock in the Transaction and an amendment to its certificate of incorporation to increase the number of authorized shares of common stock of Renovaro.

Important Additional Information and Where to Find It

In connection with the proposed Transaction, Renovaro intends to file a proxy statement (the "proxy statement"), and will file other documents regarding the proposed Transaction with the SEC. INVESTORS AND SECURITYHOLDERS OF RENOVARO ARE URGED TO CAREFULLY AND THOROUGHLY READ, WHEN THEY BECOME AVAILABLE, THE PROXY STATEMENT, AS MAY BE AMENDED OR SUPPLEMENTED FROM TIME TO TIME, AND OTHER RELEVANT DOCUMENTS FILED BY RENOVARO WITH THE SEC BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT RENOVARO, GEDI CUBE AND THE PROPOSED TRANSACTION, THE RISKS RELATED THERETO AND RELATED MATTERS.

Once complete, a definitive proxy statement will be mailed to stockholders of Renovaro. Investors will be able to obtain free copies of the proxy statement, as may be amended from time to time, and other relevant documents filed by Renovaro with the SEC (when they become available) through the website maintained by the SEC at www.sec.gov. Copies of documents filed with the SEC by Renovaro, including the proxy statement (when it becomes available), will be available free of charge from Renovaro’s website at www.renovarobio.com under the "Financials" tab.

Participants in the Solicitation

Renovaro and its directors and executive officers may be deemed to be participants in the solicitation of proxies from the stockholders of Renovaro in connection with the proposed Transaction. Information about Renovaro’s directors and executive officers is set forth in Renovaro’s definitive proxy statement for the 2023 annual meeting of stockholders filed with the SEC on May 16, 2023, and the proxy statement (when it becomes available). Other information regarding the interests of such individuals, as well as information regarding other persons who may be deemed participants in the proposed Transaction, will be set forth in the proxy statement and other relevant materials to be filed with the SEC when they become available. Stockholders of Renovaro, potential investors, and other readers should read the proxy statement carefully when it becomes available before making any voting or investment decisions.

No Offer or Solicitation

This communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval with respect to the proposed Transaction or otherwise. No offering of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act of 1933, as amended, or otherwise in accordance with applicable law.

On September 29, 2023 AbbVie (NYSE: ABBV) reported data from its Phase 3 CANOVA study evaluating the safety and efficacy of venetoclax (VENCLEXTA/ VENCLYXTO) plus dexamethasone (VenDex) for patients with t(11;14)-positive relapsed or refractory (R/R) multiple myeloma who have received two or more prior treatments (Press release, AbbVie, SEP 29, 2023, View Source [SID1234635535]). Data did not demonstrate that the treatment combination significantly improved progression-free survival (PFS), the primary endpoint of the trial. Patients receiving VenDex showed improvement in median PFS of 9.9 months compared to 5.8 months with the combination of study comparator pomalidomide and dexamethasone (PomDex); however, the results did not reach statistical significance [HR = 0.823, 95% CI: (0.596, 1.136); p-value of 0.237].

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Select prespecified secondary endpoints from the CANOVA trial include the following:

Overall response rate (ORR): 62% in VenDex vs. 35% in PomDex (nominal p-value of <0.001)
Rate of very good partial response or better (VGPR) at 39% in VenDex vs. 14% in PomDex (nominal p-value of <0.001)
Median overall survival (OS) was 32.4 months in VenDex vs. 24.5 months in PomDex [HR of 0.697 (95% CI: 0.472, 1.029); nominal p-value of 0.067]
Additional prespecified analyses include:

PFS per investigator which resulted in a median PFS of 9.1 months with VenDex vs 4.9 months with PomDex [HR = 0.737, (95% CI: 0.543, 1.000); nominal p-value of 0.050]
Median time to next treatment (TTNT) which was longer in the VenDex arm 21.2 months vs. 8.3 months in the PomDex arm [HR of 0.546 (95% CI: 0.385, 0.776); nominal p-value of 0.001]
The safety profile of the combination of venetoclax and dexamethasone in the trial was generally consistent with the known safety profiles when used as single agents and no new safety signals have emerged. The most common adverse events (AEs) experienced by patients (>20%) treated with VenDex included any infection (61%), diarrhea (41%), lymphopenia (24%) and nausea (22%). The most common AEs experienced by subjects treated with PomDex included neutropenia (63%), any infection (57%), thrombocytopenia (39%) and anemia (35%).

Multiple myeloma is the second most common blood cancer in the world.1 Many patients experience poor outcomes as most eventually relapse despite recent treatment advances. A subset of patients have the t(11;14) biomarker, the most common chromosomal translocation in multiple myeloma, that can signal an overexpression of the BCL-2 protein.2

"While the CANOVA trial did not meet its primary endpoint, given the potential favorable trends seen in the study, we will discuss these data with health authorities in the near future," said Mariana Cota Stirner, M.D., Ph.D., therapeutic area head oncology hematology, AbbVie. "We remain committed to elevating the standard of care for blood cancer patients around the world including patients with multiple myeloma."

Venetoclax is currently approved for patients with previously untreated and treated chronic lymphocytic leukemia (CLL) and newly diagnosed acute myeloid leukemia (AML). Venetoclax is not approved by any regulatory authority in any country for the treatment of multiple myeloma. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About the CANOVA Study3
CANOVA is a Phase 3, multicenter, randomized, open label study of either venetoclax or pomalidomide in combination with dexamethasone in patients with t(11;14)-positive R/R multiple myeloma. The study was initiated in 2018 and enrolled 263 patients 18 years and older with a documented diagnosis of multiple myeloma with t(11;14)-positive disease based on standard International Myeloma Working Group (IMWG) criteria, who had received at least two prior lines of therapy.

The primary endpoint of the trial was IRC-assessed PFS. Secondary endpoints include ORR, VGPR or better response rate, OS and MRD negativity rate defined at 10-5 threshold, as measured by centralized testing of bone marrow aspirate samples by next generation sequencing.

About Multiple Myeloma
Multiple myeloma is a type of blood cancer that affects plasma cells, which grow out of control and accumulate in the body’s bone marrow.1,4 Multiple myeloma is the second most common blood cancer in the world.1 An estimated 176,000 people globally were diagnosed with multiple myeloma in 2020, and 117,000 people died from the disease.5 In approximately 16% to 24% of people with multiple myeloma, t(11;14) is the most frequently seen chromosomal translocation.2

Nearly all multiple myeloma patients eventually relapse, which is associated with poor outcomes, and each remission is typically shorter than the previous one.6

About VENCLEXTA/VENCLYXTO (venetoclax)
VENCLEXTA/VENCLYXTO (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

Indication and Important VENCLYXTO ▼ (venetoclax) EU Safety Information7

Indications

Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumour lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as Venclyxto efficacy may be reduced.

Special Warnings & Precautions for Use

Tumour Lysis syndrome, including fatal events, has occurred in patients when treated with Venclyxto. For CLL and AML, please refer to the indication-specific recommendations for prevention of TLS in the Venclyxto summary of product characteristic (SmPC).

Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. The risk of TLS is a continuum based on multiple factors, including comorbidities. Venclyxto poses a risk for TLS at initiation and during the dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venclyxto and at each dose increase.

Neutropenia (grade 3 or 4) has been reported. Complete blood counts should be monitored throughout the treatment period.

In patients with AML, neutropenia (grade 3 or 4) is common before starting treatment. The neutrophil counts can worsen with Venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy. Dose modification and interruptions for cytopenias are dependent on remission status.

For CLL and AML, please refer to the indication-specific recommendations for dose modifications for toxicities in the Venclyxto SmPC.

Serious infections including sepsis with fatal outcome have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment including antimicrobials and dose interruption or reduction as appropriate.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions

In CLL and AML CYP3A inhibitors may increase Venclyxto plasma concentrations.

In CLL, at initiation and dose-titration phase, Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, please refer to the recommendations for dose modifications in the Venclyxto SmPC.

In AML, please refer to the AML-specific recommendation for dose modifications for potential interactions with CYP3A inhibitors, in the VENCLYXTO SmPC.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease Venclyxto plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions

CLL

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.

Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia.

AML

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in combination with azacitidine or decitabine in the VIALE-A and M14-358, respectively, were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite, haemorrhage, dizziness/syncope, hypotension, headache, abdominal pain, and anaemia.

The most frequently reported serious adverse reactions (≥5%) in patients receiving venetoclax in combination with azacitidine were febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358, the most frequently reported serious adverse reactions (≥5%) were febrile neutropenia, pneumonia, bacteraemia and sepsis.

Discontinuations due to adverse reactions occurred in 24% of patients treated with venetoclax in combination with azacitidine in the VIALE-A study, and 26% of patients treated with venetoclax in combination with decitabine in the M14-358 study, respectively.

Dosage reductions due to adverse reactions occurred in 2% of patients in VIALE-A, and in 6% of patients in M14-358. Venetoclax dose interruptions due to adverse reactions occurred in 72% and 65% of patients, respectively. The most common adverse reaction that led to dose interruption (>10%) of Venetoclax in VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and thrombocytopenia. The most common adverse reactions that led to dose interruption (≥5%) of venetoclax in M14-358 were febrile neutropenia, neutropenia/neutrophil count decreased, pneumonia, platelet count decreased, and white blood cell count decreased.

Special Populations

Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.

For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.

Venclyxto may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

This is not a complete summary of all safety information. See Venclyxto (venetoclax) SmPC at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

On September 28, 2023 KeYe Life Technologies reported KY1 injection preparation has completed all preclinical experiments and completed the clinical approval application of the US FDA (Press release, KeYe Life Technologies, SEP 28, 2023, View Source;article_id=85 [SID1234644611]). KY1 is a small molecule inhibitor of RNA helicase developed independently by the company. It is the first molecule of its kind (First-In-Class) and an innovative drug product transformed from the company’s independent scientific research.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.