On September 4, 2023 Oncorena reported first patient treated in the Phase I/II trial of the first-in-class compound, ONC175 (orellanine), in patients with metastatic renal cancer and dialysis (Press release, Oncorena, SEP 4, 2023, View Source [SID1234634865]). The first treatment was conducted on August 8 without any complication at the Center for Clinical Cancer studies at Karolinska University Hospital, Stockholm, Sweden. The study examines safety, tolerability, pharmacokinetics and anti-tumor effect when treated with ONC175.

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"I am happy to announce first patient, first treatment in our clinical phase I/II trial, Oncorella-1, with ONC175 (orellanine). This is a milestone for Oncorena accelerating our development plan since these patients are in need of more effective therapies," said Börje Haraldsson, CEO and CSO at Oncorena AB.

The clinical study, Oncorella-1, is conducted at the Center for Clinical Cancer Studies at Karolinska University Hospital, Stockholm, Sweden. Hemodialysis is given at the same hospital, since patients eligible to the study are dialysis-dependent. Now, the first patient was given an infusion of ONC175 for 30 minutes. Additional patients are ready for treatment in the autumn. Each patient is followed up four weeks after the infusion by an independent Data Review Committee recommending potential dose escalations.

The drug candidate ONC175 has a unique mode of action and is being developed as a potential cure in patients with metastatic renal cancer and dialysis-dependent renal failure. Preclinical studies have shown that ONC175 is highly selective organ-targeted chemotherapy with potent anti-tumor effects metastatic renal cancer.

"It concerns a very different and unique medicine that is being tested here on patients with disseminated kidney cancer. We are very happy that the study is underway and we look forward to the results," says Jeffrey Yachnin, M.D. responsible for the study at the Center for Clinical Cancer Studies, Karolinska University Hospital.

This Press Release concerns a drug candidate under development. It does not attempt to communicate any conclusions regarding effect or safety. It is the purpose of clinical trials to objectively assess safety, tolerability and effects of drug candidates. There is no guarantee that the drug candidate’s development program will be completed or that it will gain approval by relevant authorities.

About ONC175

ONC175 with its new and unique mode of action, is being developed for organ-specific chemotherapy with curative potential for patients with metastatic renal cancer. ONC175 is the synthetically produced drug product, which active component is orellanine. Orellanine is found in mushrooms of the Cortinarius family. These can accidentally be picked and eaten as they are mistaken for funnel chanterelles. The clinical effects of orellanine are well documented and highly specific for kidneys. ONC175 is expected to have effects on the two most common forms of renal cancer, i.e., the clear cell och papillary types, representing approximately 90 percent of cases.

About the Phase I/II clinical trial

The Phase I/II clinical trial of ONC175 (orellanine), Oncorella-1, enrolls patients with metastatic renal cancer on dialysis due to renal failure. The study is conducted at the Centre for Clinical Cancer Studies at the Karolinska University Hospital in Stockholm, Sweden, and studies safety, tolerability, pharmacokinetics and signs of anti-tumour effects in treatment with ONC175. The Phase I/II trial will include up to 40 patients and may include patients from other countries.

About kidney cancer

Approximately 400,000 patients are affected by kidney cancer globally according to the WHO. The disease can often be cured by surgery if detected early, but the prognosis is less favourable if there are metastases. Today, the disease is treated with various types of targeted and immuno-active drugs, that seldom are curative. There is therefore a great and urgent unmet medical need for new, effective and safe drugs.

On September 4, 2023 QIAGEN reported that it will host the Global Oncohematology Summit 2023, held on September 13 and 14, under the theme "I Can: Improving Patients’ Lives Through Oncohematology Testing and Research" (Press release, Qiagen, SEP 4, 2023, View Source;Improving-patients-lives-through-testing-and-research-/default.aspx [SID1234634863]). The virtual event unites experts and patients from around the globe to discuss the latest advances and challenges in oncohematology testing, blood cancer clinical care, and research, focusing on improving patient outcomes. Emphasizing the utmost importance of patients’ perspectives, the summit will feature their testimonies, bringing their voices and considerations to the forefront of the discussion.

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Blood cancer continues to pose a significant global threat, with more than 470,000 new cases of leukemia in 2020 alone and nearly 312,000 deaths . With an overall 5-year relative survival rate in the US of 66.4% for all types of leukemia , early diagnosis and treatment are more crucial than ever. The Global Oncohematology Summit 2023 will be a vital platform for blood cancer clinical researchers, oncohematologists, data specialists, and survivors to exchange innovative ideas and insights in testing, clinical care and research.

"The QIAGEN Global Oncohematology Summit underscores our dedication to improving patient outcomes through collaboration, innovation, and education," said Jonathan Arnold, Vice President, Head of Translational Science and Precision Diagnostics at QIAGEN. "By bringing together experts from around the world, we aim to address the challenges that impact diagnosis, monitoring, and patient care, and ultimately, make a difference in the lives of those affected by blood cancers."

The event’s keynote speaker, Prof. Elias Jabbour, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, USA, said: "It is important to discuss and share the most innovative therapies in hematology from leukemia to myeloma, including assessing and managing measurable residual disease. There will be plenty of time for questions and answers and panel discussions where experts from around the globe will exchange their experiences."

The QIAGEN Global Oncohematology Summit 2023, which is expected to gather over 500 participants from across the world, is a free, educational virtual event that is CME and CPD-accredited. Event highlights include a diverse range of topics such as the latest blood cancer patient therapies management, expert views on CAR-T cell therapy and other breakthroughs, advocate and patient perspectives, new insights into testing and monitoring blood cancer and a European diagnostic laboratory’s perspective on their IVDR strategy.

To join the QIAGEN Global Oncohematology Summit on September 13 and 14, please register here.

QIAGEN: Advancing cancer diagnostics and research

Due to the vast biological and genetic diversity of hematological malignancies, identifying crucial molecular markers is essential for advancing blood cancer precision medicine and research. QIAGEN provides an extensive portfolio, encompassing sample collection to data interpretation. For example, the ipsogen assays provide diagnostic solutions, focusing on the detection of specific genetic and molecular biomarkers. These tests enable personalized care, early detection, treatment selection, response and monitoring, leading to more informed decisions and better patient care. QIAGEN ipsogen tests allow healthcare professionals to tailor treatment plans, assess measurable residual disease, and provide enhanced prognostic capabilities.

QIAGEN is also collaborating with more than 30 global pharmaceutical and biotechnology companies to develop and market companion diagnostics, which detect clinically relevant genetic abnormalities and provide insights that guide clinical decision-making in diseases like blood cancers. QIAGEN has an unmatched depth and breadth of technologies, from next-generation sequencing (NGS) to polymerase chain reaction (PCR) and digital PCR (dPCR) for companion diagnostic development.

You can find out more about QIAGEN’s blood cancer portfolio here.

On September 4, 2023 Genmab A/S (Nasdaq: GMAB) and Seagen Inc. (Nasdaq: SGEN) reported that the Phase 3 innovaTV 301 global trial in recurrent or metastatic cervical cancer patients with disease progression on or after front-line therapy who received TIVDAK (tisotumab vedotin-tftv), compared with chemotherapy alone, met its primary endpoint of overall survival (OS) (Press release, Genmab, SEP 4, 2023, View Source [SID1234634862]). An Independent Data Monitoring Committee determined that OS crossed the pre-specified efficacy boundary at interim analysis. The key secondary endpoints of investigator-assessed progression-free survival and objective response rate also demonstrated statistical significance. The safety profile of TIVDAK in innovaTV 301 is consistent with the known safety profile of TIVDAK as presented in the U.S. prescribing information, and no new safety signals were observed.

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The results of innovaTV 301/ENGOT cx-12/GOG 3057, a global, randomized, open-label Phase 3 trial, add to the previous results of innovaTV 204, which served as the basis for the accelerated approval of TIVDAK in the United States. Subject to discussions with regulatory authorities, the results from innovaTV 301 are intended to serve as the pivotal confirmatory trial for the U.S. accelerated approval and support global regulatory applications. The innovaTV 301 China extension study has been initiated and continues to enroll patients, in collaboration with Zai Lab Limited.

"TIVDAK is the only U.S. Food and Drug Administration-approved therapy in second-line recurrent or metastatic cervical cancer regardless of biomarker status, tumor histology and prior therapy," said Roger Dansey, M.D., President of Research and Development and Chief Medical Officer at Seagen. "Demonstrating a survival benefit with the results of innovaTV 301 is a critical milestone in our efforts to ensure more adults living with advanced cervical cancer have an approved treatment option."

"With limited options for advanced cervical cancer patients who have progressed after front-line therapy, there is a need for therapeutic options with new mechanisms of action, particularly those with a demonstrated survival benefit," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "These results provide hope for patients with recurrent or metastatic cervical cancer."

Results of the Phase 3 innovaTV 301 clinical trial will be submitted for presentation at an upcoming medical congress and discussed with regulatory authorities.

About Cervical Cancer
Cervical cancer remains a disease with high unmet need despite advances in effective vaccination and screening practices to prevent and diagnose pre-/early-stage cancers for curative treatment. Recurrent and/or metastatic cervical cancer is a particularly devastating and mostly incurable disease; up to 16% of adults are diagnosed with metastatic disease at diagnosisi,ii and, for adults diagnosed at earlier stages who receive treatment, up to 61% will experience disease recurrence and progress to metastatic cervical cancer.iii It is estimated that in 2023, more than 13,960 new cases of invasive cervical cancer will be diagnosed in the U.S. and 4,310 adults will die from the disease.iv

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, randomized, open-label Phase 3 trial evaluating TIVDAK (tisotumab vedotin-tftv) versus investigator’s choice of chemotherapy alone (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received no more than two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with a standard of care systemic chemotherapy doublet or platinum-based therapy (if eligible) are included. The main efficacy outcome measure is overall survival. The main secondary outcomes are progression-free survival, objective response rate, time to response and duration of response, as assessed by the investigator, as well as safety and quality of life outcomes.

The study was conducted by Seagen in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057). For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About TIVDAK (tisotumab vedotin)
TIVDAK (tisotumab vedotin) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Determination of TF expression is not required. Nonclinical data suggest that the anticancer activity of TIVDAK is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for TIVDAK in adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is the first and only approved ADC for the treatment of these patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The Phase 3 innovaTV 301 clinical trial, an open-label, randomized, global trial, is intended as the confirmatory trial for use in verifying and describing the clinical benefit and for global regulatory applications.

Indication
TIVDAK is indicated in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY

TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

WARNINGS AND PRECAUTIONS

Ocular adverse reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8% of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam, including visual acuity and slit lamp exam, at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.

Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or central nervous system (CNS) hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis that is severe, life-threatening, or fatal can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Symptoms may include hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations. Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Severe cutaneous adverse reactions, including events of fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur in patients treated with TIVDAK.

Monitor patients for signs or symptoms of severe cutaneous adverse reactions, which include target lesions, worsening skin reactions, blistering or peeling of the skin, painful sores in mouth, nose, throat, or genital area, fever or flu-like symptoms, and swollen lymph nodes. If signs or symptoms of severe cutaneous adverse reactions occur, withhold TIVDAK until the etiology of the reaction has been determined. Early consultation with a specialist is recommended to ensure greater diagnostic accuracy and appropriate management. Permanently discontinue TIVDAK for confirmed Grade 3 or 4 severe cutaneous adverse reactions, including SJS.

Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions
Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug Interactions
Strong CYP3A4 inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or severe hepatic impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

Please see full prescribing information, including BOXED WARNING for TIVDAK here.

On September 4, 2023 Circio Holding ASA (OSE: CRNA), a biotechnology company developing novel circular RNA and immunotherapy medicines, reported that the completed phase 1/2 trial of ONCOS-102 in combination with Standard of Care (SoC) chemotherapy in malignant pleural mesothelioma (MPM) has been published in the Journal for ImmunoTherapy of Cancer (JITC), the prestigious immunology journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Circio, SEP 4, 2023, View Source [SID1234634861]).

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The study was a randomized phase 1/2 trial adding ONCOS-102 to SoC chemotherapy (pemetrexed/cisplatin) in first and later line MPM to assess safety, immune activation and clinical efficacy in a total of 31 patients. The ONCOS-102 and SoC combination showed a favorable safety profile, robust immune responses in injected tumors and a signal of clinical benefit. In first line patients, the OS rate at 30 months was 34.1% for ONCOS-102-treated patients, which is a clear improvement over the first-line SoC-only control group where the OS rate was 0%.

Title of publication: ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment

For the full publication, please see link: View Source

Margrethe Sørgaard, VP and Head of Clinical at Circio, said: "Mesothelioma remains a challenging disease with poor prognosis and few available treatment options. In this exploratory trial, ONCOS-102 demonstrated a clear signal of clinical benefit for this underserved patient group, particularly in an early treatment setting. Importantly, the study also showed that ONCOS-102 can be safely and effectively combined with chemotherapy and drive robust immune activation in an immunologically cold tumor type, thereby demonstrating the versatility of the product and expanding future development opportunities."

On September 4, 2023 Celyad Oncology (Euronext: CYAD) (the "Company" or "Celyad Oncology"), reported its financial results and recent business developments for the first half year, ended June 30, 2023 (Press release, Celyad, SEP 4, 2023, View Source [SID1234634860]).

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"Celyad Oncology is now fully focused on maximizing the potential of its proprietary technology platforms and intellectual property, enabling the Company to be at the forefront of developing next-generation CAR T-cell therapies. We are eager to see the impact of our research efforts on the future of CAR T-cell treatments, with the goal to broaden the range of cancer indications and tackle the main limitations of current CAR T-cell therapies" commented Georges Rawadi, Celyad Oncology’s Chief Executive Officer.

First Half 2023 and recent corporate highlights:

Georges Rawadi was appointed Chief Executive Officer of the Company as from April 27, 2023. Georges Rawadi is a seasoned executive with over 20 years of experience in pharma/biotech, as research director, business developer, CEO, and board member. He also has insightful knowledge of both the company and the CAR-T space as he spent four years at Celyad Oncology (2014-2018) as Vice-President Business Development & Intellectual Property ("BD & IP"). Georges Rawadi has a genuine passion for seeking and creating new business opportunities.
On May 5th, 2023, the Company announced voluntary delisting of its American Depositary Shares representing ordinary shares ("ADSs") from the Nasdaq Global Market. Delisting was effective as of July 20, 2023. The Company continues to be listed on Euronext Brussels and Euronext Paris.
On August 24, 2023, the Company announced that it has obtained commitments from Fortress, Tolefi and other longstanding existing shareholders to subscribe to a capital increase of up to €9.8 million in 2 tranches:
A first tranche of 2.0 million was disbursed in the context of authorized capital as of September 4, 2023; and
A second tranche to be subscribed by Fortress is subject to the approval by the extraordinary shareholders’ meeting. Following this private placement, the Company believes that its existing cash and cash equivalents should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the end of the fourth quarter of 2024.
First Half 2023 and recent operational highlights:

Short hairpin ribonucleic acid (shRNA) non-gene edited technology – During this first half of 2023, we have collected and presented data validating our shRNA multiplexing approach:
We developed a micro-RNA (miRNA)-based multiplex shRNA platform designed for easy, efficient, and tunable downregulation of up to four target genes simultaneously;
We showed that the downregulation of each target gene could be fine-tuned, from a moderate downregulation up to a functional knock-out, without the need of gene editing thereby avoiding associated potential safety issues;
The plug-and-play design of our platform is designed to allow swapping of each target sequence without affecting the performance of the technology and streamlining of the generation of engineered adoptive T-cell therapies;
To demonstrate the effectiveness of our approach, we have been able to simultaneous knock-down in CAR T-cells several genes involved in different cellular processes such as alloreactivity (CD3ζ), cell persistence (β2M, CIITA), T-cell exhaustion (PD-1, LAG-3), or ligand-induced apoptosis (CD95);
Data were presented at the World Oncology Cell Therapy Congress in Boston, US (April 25-26, 2023) and at the CAR-TCR Summit in Boston, US (August 29 – September 1).
NKG2D-based CAR T-cells and multi-specific CAR T-cell platform – During this first half of 2023, we have published data validating our NKG2D-based CAR T-cell approach and presented data from our multi-specific CAR T-cell platform:
Results from 16 patients treated in the dose-escalation segment of the hematological arm of the Phase I THINK trial were published in The Lancet Haematology Journal (Lancet Haematol. 2023 Mar;10(3):e191-e202) and provided proof-of-concept for targeting NKG2D ligands (NKG2DL) with CAR T-cell therapy;
We have developed different CD19/NKG2DL multi-specific CAR T-cells, utilizing both tandem and dual NKG2D-based CARs that encompass the extracellular domain of the natural NKG2D receptor fused to an anti-CD19 scFv, or co-expressed with an anti-CD19 CAR, respectively;
The majority of our CD19/NKG2DL multi-specific CAR T-cell candidates were able to secrete cytokines, proliferate, and eliminate acute lymphoblastic leukemia tumor cells lacking the CD19 antigen in vitro. Interestingly, some of these multi-specific CAR T-cells displayed a better in vitro functionality against wild-type leukemia tumor cells expressing the CD19 antigen as compared to CD19-specific single targeting CAR T-cells, highlighting the potential of our approach against both CD19 positive and CD19 negative cancer cells;
First in vivo data suggest that our CD19/NKG2DL multi-specific CAR T-cell candidates have an enhanced anti-tumor efficacy against heterogeneous lymphoma tumors as compared to currently existing treatment options;
We are currently developing several NKG2D-based multi-specific CAR T-cells for the treatment of diverse solid cancers where there is a high heterogeneity in antigen expression;
Data were presented at the Immuno-Oncology Summit Europe 2023 held in London, UK (June 20-22, 2023).
Upcoming anticipated milestones

More data and evidence in the context of the multi-specific CAR platform and shRNA multiplexing approach in H2 2023, with the aim of a clinical evaluation of assets and initiation of clinical trials either by the Company and/or through strategic partnerships afterwards;
Relocation, in H2 2023, into a new research facility which fits better its current needs after the strategic shift. The Company will remain headquartered at the Axis Parc, Mont-Saint-Guibert, Belgium but with its new business location at Dumont 9.
Upcoming Conferences

The Company will take part in the 4th International Conference on Lymphocyte Engineering (ICLE) in Munich (September 12-14) and the annual congress of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego (November 1-5), as well at several business conferences in the second half of 2023.
First Half 2023 Financial Results

Key financial figures for the first half of 2023, compared with the first half of 2022 and full year 2022, are summarized below:

The Company’s license and collaboration agreements generated no revenue in the first half of 2023 similar to the first half of 2022.

The Research and Development (R&D) expenses have decreased primarily due to the Company’s decision to discontinue some of preclinical programs and manufacturing and clinical study activities after the Company’s decision to adopt and implement a new business strategy. Furthermore, there has been a decrease of employee expenses and related travel costs which is mainly related to headcount reduction through 2022, to support the Group’s reorganization around preclinical and clinical programs, as well as a decrease of the expenses associated with share-based payments (non-cash expenses) related to the warrant plan offered to the Company’s employees, managers and directors.

General and Administrative (G&A) expenses were €3.7 million in 2023 as compared to €6.2 million in 2022. This decrease is primarily related to lower insurances costs, the decrease of employee expenses due to headcount reduction and management changes through 2022 to support the Company’s reorganization and the decrease of the expenses associated with the share-based payments (non-cash expenses) related to the warrants plan offered to the Company’s employees, managers and directors.

As of June 30, 2023, there was no change in fair value of the contingent consideration and other financial liabilities as Management has determined that there have been no event (such as a firm sublicense or collaboration contract) that increases the probability of the projected future cash outflow due to Celdara Medical, LLC and Dartmouth College, indicating that the probability is remote, similar to December 31, 2022.

Regarding the other income/other expenses, the Company recorded €2.1 million in net other income for the first half of 2023 compared to a net other income of €1.6 million for the first half of 2022. The net other income for the first half of 2023 is primarily due to the gain on the sale of certain fixed assets to Cellistic for €1.1 million and grant income from the Walloon Region of €0.8 million.

Net loss was €3.7 million, or €(0.17) per share, for the first half of 2023 compared to a net loss of €14.1 million, or €(0.62) per share, for the same period of 2022.

Net cash used in operations, was €8.3 million for the first half of 2023 compared to €16.3 million for the first half of 2022. The decrease of €8.0 million is primarily driven by the sale of the manufacturing activities in 2022 combined with global decrease on preclinical and clinical activities, insurance costs, headcount, management changes costs and associated impact on the change in working capital.

As of June 30, 2023, the Company had cash and cash equivalents of €5.0 million. No capital increase has occurred in the first half of 2023.

As of June 30, 2023, the total number of basic shares outstanding were 22.6 million similar to December 31, 2022.

Conference Call and Webcast Details

A conference call will be held on Tuesday 5th of September at 1:00 p.m. CET / 7:00 a.m. EDT discuss half year 2023 financial results and provide an update on the Company’s recent changes and upcoming milestones.

Participants may access the conference call by dialing +1-877-407-9716 or +1-201-493-6779 (United States, International), +32 (0) 800-73-904 (Belgium Fixed) or +32 (0) 800-73-566 (Belgium Mobile). Participants may ask for instant telephone access to the event via the "Call me" link or attend the conference live webcast.

Archived recording will be available in the "Events" section of the Celyad website after the event.

Financial Calendar 2023

November 9th, 2023 Third Quarter 2023 Business Update
The financial calendar is communicated on an indicative basis and may be subject to change.