On November 22, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) approved Libtayo (cemiplimab) as monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer and disease progression on or after platinum-based chemotherapy (Press release, Regeneron, NOV 22, 2022, View Source [SID1234624321]).

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"Despite recent advancements in the prevention and treatment of cervical cancer, there remain limited options for people with recurrent or metastatic cases," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "Libtayo was the first PD-1 inhibitor to demonstrate significant improvements in survival compared to chemotherapy in a Phase 3 trial. With this fourth approval from the European Commission, Libtayo can now be extended to appropriate patients in the European Union with advanced cervical cancer, irrespective of their PD-L1 status or histology."

The EC approval in advanced cervical cancer is based on data from the global Phase 3 EMPOWER-Cervical 1 trial, which was conducted with the GOG Foundation, Inc. (GOG), the European Network for Gynaecological Oncological Trial groups (ENGOT) and NRG Oncology-Japan. The trial evaluated Libtayo in comparison to an investigator’s choice of chemotherapy and enrolled 608 patients across 14 countries, irrespective of PD-L1 expression status or histology. In March 2021, the trial was stopped early based on the highly significant effect of Libtayo on overall survival (OS) among squamous cell carcinoma (SCC) patients following a unanimous recommendation by the Independent Data Monitoring Committee.

"Consistent with our mission to bring the best treatments to patients across Europe living with gynaecological cancers, we are proud to have been a part of the landmark ENGOT-cx9/GEICO/EMPOWER Cervical-1 trial for Libtayo," said Professor Ignace Vergote, investigator and gynecologist oncologist at University Hospitals Leuven in Belgium, and Vice-Chair of the Trial Steering Committee. "Libtayo is an important advancement for patients with recurrent or metastatic cervical cancer whose disease has progressed following platinum-based chemotherapy and could offer a new standard of care in this setting. We are grateful to those who participated in the trial and to our partners at Regeneron, ENGOT, the GOG Foundation and NRG Oncology-Japan without whom this approval would not have been possible."

Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed between the ages of 35 and 44. Approximately 600,000 new cases of cervical cancer and 350,000 deaths from cervical cancer occur worldwide each year. Almost all cases are caused by human papillomavirus (HPV) infection, with approximately 80% classified as squamous cell carcinoma (SCC; arising from cells lining the external portion of the cervix) and the remainder largely adenocarcinomas (arising from glandular cells lining the internal portion of the cervix). Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced stages.

In addition to today’s approval, Libtayo is approved in the European Union (EU) for the treatment of certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced non-small cell lung cancer (NSCLC).

About the Phase 3 Trial
EMPOWER-Cervical 1 was an open-label, multi-center Phase 3 trial that investigated Libtayo monotherapy versus an investigator’s choice of commonly used chemotherapy in patients with recurrent or metastatic cervical cancer who had progressed on platinum-based chemotherapy. Patients (median age: 51 years) were randomized to receive Libtayo (350 mg every three weeks) or chemotherapy (pemetrexed, vinorelbine, topotecan, irinotecan or gemcitabine). The primary endpoint for the trial was OS, analyzed first among patients with SCC, then in the total population.

Patients were allowed to enroll regardless of PD-L1 expression status, with 78% of patients having SCC and 22% having adenocarcinoma or adenosquamous carcinoma. The trial included women from 14 countries: Australia, Belgium, Brazil, Canada, Greece, Italy, Japan, Poland, Russia, South Korea, Spain, Taiwan, the UK and the U.S.

Results from the trial demonstrated that those treated with Libtayo (n=304) compared to chemotherapy (n=304) experienced significant improvements in OS, progression-free survival (PFS) and objective response rate (ORR) including a:

31% reduction in the risk of death and a longer median OS in the overall population (12.0 months Libtayo, 8.5 months chemotherapy; hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.56 to 0.84; p=0.00011).
27% reduction in the risk of death and a longer median OS in patients with SCC histology (11.1 months Libtayo, 8.8 months chemotherapy; HR: 0.73; 95% CI: 0.58 to 0.91; p=0.00306).
25% reduction of risk in progressive disease in the overall population (HR: 0.75; 95% CI: 0.62 to 0.89; p=0.00048).
16% ORR for Libtayo, versus 6% for chemotherapy in the overall population (95% CI: 12.5 to 21.1 vs. 3.8 to 9.6).
Safety was assessed in 1,281 patients with advanced solid malignancies who received Libtayo monotherapy in five clinical studies. The median duration of exposure to Libtayo was 28 weeks (range: 2 days to 144 weeks). Immune-mediated adverse reactions occurred in 21% of patients treated with Libtayo and led to permanent discontinuation in 4.6% of patients. The most common immune-mediated adverse reactions were hypothyroidism (6.8%), hyperthyroidism (3.0%), immune-mediated pneumonitis (2.6%), immune-mediated hepatitis (2.4%), immune-mediated colitis (2.0%) and immune-mediated skin adverse reactions (1.9%). Adverse events were serious in 32.4% of patients and led to permanent discontinuation in 9.4% of patients. The grade 3 or higher adverse events occurring in >1% of patients were anaemia (5.2%), hypertension (2.6%), fatigue (2.6%), urinary tract infection (2.3%), hepatitis (1.8%), musculoskeletal pain (1.8%), rash (1.6%) dyspnea (1.2%) and pneumonitis (1.1%). No new Libtayo safety signals were observed.

Results from the trial were previously published in the New England Journal of Medicine.

About Regeneron in Oncology
At Regeneron, we’re applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer. Our oncology portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.

If you are interested in learning more about our clinical trials, please contact us ([email protected] or 844-734-6643) or visit our clinical trials website.

About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron’s proprietary VelocImmune technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries, Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced non-small cell lung cancer (NSCLC), as well as in advanced cervical cancer in the EU, Canada and Brazil. As of July 1, 2022, Libtayo is developed and marketed globally by Regeneron.

In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Outside of the U.S. the generic name of Libtayo in its approved indication is cemiplimab.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:

People with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
People with a type of skin cancer called basal cell carcinoma (BCC):
That cannot be removed by surgery (locally advanced BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI.
That has spread (metastatic BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
Adults with a type of lung cancer called NSCLC:
Libtayo may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor does not have an abnormal "EGFR", "ALK" or "ROS1" gene.
Libtayo may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor tests positive for high "PD-L1", AND your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately one in five of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?
LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider will give you a pregnancy test before you start treatment
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk with your healthcare provider about birth control methods that you can use during this time
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO
are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of LIBTAYO when used alone include muscle or bone pain, tiredness, rash, and diarrhea. The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, decreased appetite. These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296.

On November 14, 2022 Targovax ASA (OSE: TRVX) and Hubro Therapeutics AS (Hubro) reported that they have entered into an asset purchase agreement whereby Hubro acquires Targovax’s GM-CSF (Granulocyte macrophage colony-stimulating factor) process development and production project (Press release, Hubro Therapeutics, NOV 14, 2022, View Source [SID1234624320]).

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Under the agreement, Hubro will make a cash payment to Targovax of 10MNOK for the acquisition of the GM-CSF project. Targovax retains conditional buy-back and supply options, and a share in gross proceeds in the event of a re-sale of the asset within a time-limited period.

Jon Amund Eriksen, Chief Executive Officer of Hubro, said: "For the commercial development of our therapeutic and prophylactic cancer vaccines it is important for us to have full control over production and supply of all pharmaceutical active components, including GM-CSF. We are therefore delighted for having the opportunity to take over the GM-CSF development project from Targovax, which will provide significant savings of development costs and time towards obtaining the high-quality product we need for pivotal clinical development and later marketing of our cancer vaccines."

GM-CSF is an immuno-modulator used for protein and peptide-based vaccines and was the adjuvant component of Targovax’s first generation mutant RAS TG vaccine products. Following a collaboration agreement with Agenus Inc. [NASDAQ: AGEN] announced earlier in 2022, Targovax will develop its next generation mutant RAS TG vaccines with Agenus ́ proprietary adjuvant QS-21 STIMULON. Two clinical trials with Targovax ́s lead mutant RAS candidate TG01 adjuvanted by QS-21 STIMULON are expected to open during 2022. The GM-CSF asset purchase agreement with Hubro ensures the continued development of the GM-CSF adjuvant product, which will serve as an integral part of Hubro’s technology platform. Hubro aims at introducing its own developed GM-CSF product in clinical testing as an adjuvant for its peptide cancer specific vaccines in 2024.

On November 22, 2022 GSK plc (LSE/NYSE: GSK) reported it has initiated the process for withdrawal of the US marketing authorisation for Blenrep (belantamab mafodotin-blmf) following the request of the US Food and Drug Administration (FDA) (Press release, GlaxoSmithKline, NOV 22, 2022, View Source [SID1234624319]). This request was based on the previously announced outcome of the DREAMM-3phase III confirmatory trial, which did not meet the requirements of the FDA Accelerated Approval regulations. Blenrep is a monotherapy treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

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As part of the Company’s efforts to ensure physicians and patients are supported during this important time, patients already enrolled in the Blenrep Risk Evaluation and Mitigation Strategy (REMS) programme will have the option to enrol in a compassionate use programme to continue to access treatment. Further information on how to enrol patients into the compassionate use program will be provided directly to REMS enrolled prescribers. Patients currently being treated with Blenrep should consult their healthcare provider.

GSK continues to believe, based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development programme, that the benefit-risk profile of belantamab mafodotin remains favourable in this hard-to-treat RRMM patient population. Patients responding to belantamab mafodotin experienced durable clinical benefit, and safety remains consistent with the known safety profile.

Sabine Luik, Chief Medical Officer, said, "We respect the Agency’s approach to the accelerated approval regulations and associated process. Multiple myeloma is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial programme and work with the US FDA on a path forward for this important treatment option for patients with multiple myeloma."

Additional trials within the DREAMM clinical trial programme are designed to determine the benefit of belantamab mafodotin in combination treatment with novel therapies and standard-of-care treatments in earlier lines of therapy and dosing optimisation to maintain efficacy while reducing corneal events. Data from the DREAMM-7 and DREAMM-8 phase III trials are event-driven, and results are anticipated in the first half of 2023. Results of these trials will be shared with health authorities and inform future regulatory pathways.

About DREAMM-3

The DREAMM-3 phase III trial is an open-label, randomised head-to-head superiority trial evaluating the efficacy and safety of single-agent belantamab mafodotin compared to pomalidomide in combination with low-dose dexamethasone (PomDex) in patients with RRMM. A total of 325 participants were randomised in a 2:1 ratio to receive either single-agent belantamab mafodotin administered as a 2.5 mg/kg dose every three weeks or PomDex. Pomalidomide was administered daily on days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (days 1, 8, 15, and 22 of each cycle). The primary endpoint was PFS. Secondary endpoints include overall survival, safety, ORR, duration of response and assessment of minimal residual disease.

About DREAMM-7

DREAMM-7 is evaluating the safety and efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone versus daratumumab in combination with bortezomib and dexamethasone.

About DREAMM-8

DREAMM-8 is assessing the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone compared with that of a combination of pomalidomide, bortezomib and dexamethasone in participants with relapsed/refractory multiple myeloma.

About multiple myeloma

Multiple myeloma is the second most common blood cancer in the US and is generally considered treatable but not curable.1,2 In the US, more than 32,000 people are estimated to be diagnosed with multiple myeloma this year, and nearly 13,000 people will die from the disease.3 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.4

About B-cell maturation antigen (BCMA)

The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway is important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients, and BCMA membrane expression is universally detected in myeloma cell lines.5

About Blenrep

Blenrep is an antibody-drug conjugate comprising a humanised BCMA monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Refer to the BLENREP Prescribing Information for a full list of adverse events and the complete important safety information in the US.

GSK in oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, and antibody-drug conjugates, either alone or in combination.

On November 22, 2022 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, reported financial results for the third quarter of 2022, ending September 30, 2022, and provided an update on clinical and corporate progress (Press release, Vivoryon Therapeutics, NOV 22, 2022, View Source [SID1234624318]).

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"In the third quarter of 2022, we were very pleased to have strengthened our financial position with a successful private placement of up to EUR 30 million. Vivoryon is happy to welcome our new investor, KKR affiliate Memory Investments, while receiving continued support from our existing and longstanding investors. Our extended financial runway allows us to continue our focus on clinical development of varoglutamstat in Alzheimer’s disease as we see progress in both our VIVIAD and VIVA-MIND trials in Europe and the U.S., respectively," said Ulrich Dauer, CEO of Vivoryon. "We are happy to report that we have completed enrollment for VIVIAD as planned. Given the recent challenges observed within the broader Alzheimer’s disease space, we believe it is a critical time for Vivoryon to evaluate how we are optimizing our clinical development programs for varoglutamstat as we work to provide meaningful benefit to our patients and their families. We are incredibly pleased with the safety profile of varoglutamstat observed to-date and are happy to share new updates to the program development today. We have carefully crafted a well-defined clinical development strategy and are pursuing a differentiated regulatory path to a potential approval for varoglutamstat with options for surrogate markers, reflecting patient benefit beyond the simple endpoint of plaque-removing potential. By utilizing both VIVIAD and VIVA-MIND to inform each respective trial, we expect to reach an exceptionally high level of clinical information for varoglutamstat."

Portfolio Highlights (Q3 2022 and post-period)

VIVIAD

VIVIAD (NCT04498650) is a state-of-the-art Phase 2b study conducted in Europe and designed to evaluate the safety, tolerability and efficacy of varoglutamstat in 250 subjects with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD).
VIVIAD has completed enrollment as planned. Overall, 259 patients at 22 study centers in five European countries have been randomized into the study. The Company will continue to evaluate primary and secondary outcome measures, which include multiple cognitive, safety and biomarker endpoints. As previously guided, Vivoryon anticipates final follow-up visits in the second half of 2023. Given the flexibility built into the study protocol, the Company has decided to enable additional follow-up visits through year-end 2023, allowing for additional data collection and longer average treatment duration of participants. Consequently, Vivoryon anticipates the average treatment duration to be approximately 82 weeks, making it one of the longest treatment durations for a large patient set within the AD clinical trial field. These changes are expected to provide Vivoryon with a larger and more meaningful set of data at the conclusion of the trial.
Vivoryon now expects to report full data, including additional follow-up data, in the first quarter of 2024.
VIVA-MIND

VIVA-MIND (NCT03919162) is a combined Phase 2a/b study for varoglutamstat conducted in the U.S. which seeks to enroll 180 patients with early AD into the Phase 2a adaptive dose finding part. About two thirds of the first cohort (600mg BID) have been treated to date with no adverse events of special interest (AESI) observed. Based on these encouraging findings, which corroborate VIVIAD study safety data, Vivoryon now plans to treat all 180 patients for at least 72 weeks, allowing for the opportunity to progress more seamlessly to a potential Phase 3 study. Using VIVA-MIND as an informed trial allows for more optionality with further advancement in clinical development while taking learnings from VIVIAD and other developments in the field into account.
The primary endpoint for this study is the CDR-SB (clinical dementia rating scale – sum of boxes) score, an established approvable endpoint measuring a combination of cognitive abilities and activities of daily living. The study is coordinated by the Alzheimer’s Disease Cooperative Study (ADCS) and supported by a USD 15 million grant from the National Institute on Aging (NIA award number R01AG061146).
All 180 patients included in the Phase 2a portion of VIVA-MIND will now continue to be treated for 72 weeks to increase quality and robustness of data and potentially allowing for a seamless transfer into a confirmatory Phase 3 study, if required. This prudent adaption is designed to increase the probability of success of the VIVA-MIND study towards potential approval. Consequently, Vivoryon is no longer guiding towards an interim futility analysis as basis for a stage-gate decision. The Company intends to provide a status update on the study in the first quarter of 2023.
Preclinical Programs

In October 2022, Nature Communications issued a joint publication of Vivoryon and Fraunhofer IZI and Monash University, Melbourne, Australia, "Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor." This article outlines the protein’s involvement in tissue homeostasis by influencing inflammation, immunity, and extracellular matrix remodeling. Dysregulation of this protein family leads to many severe diseases that we aim to treat within our pipeline, including acute kidney injury, inflammatory disease, and some cancers. Deepening our understanding of meprin α’s structure will strongly support our research and development program for selective and highly potent small molecule meprin inhibitors.
Corporate Development Highlights (Q3 2022 and post-period)

On September 30, 2022, the Company entered into a private placement of 2,054,796 registered shares at an offering price of EUR 7.30 per share. The new shares from the capital increase represent 9.3% of Vivoryon’s existing share capital and have been issued from the Company’s authorized capital under exclusion of the existing shareholders’ pre-emptive rights. Consequently, the Company’s issued share capital has increased to EUR 24,105,278.00 on completion of the private placement. In addition, the investors will have the option to purchase, in aggregate, up to another 2,054,796 registered shares at a price of EUR 7.30 during a period ending twelve months after the date of the approval of an EU Recovery Prospectus or three months after the achievement date of a defined clinical milestone, whichever is later. The gross proceeds of the private placement amount to EUR 15.0 million, and up to an additional EUR 15.0 million will be raised if the option to purchase the additional shares is exercised in full. Vivoryon intends to use the net proceeds from the offering to support the ongoing clinical development of its lead candidate varoglutamstat, currently in Phase 2 in Europe and the United States for the treatment of patients with Alzheimer’s disease, as well as for general corporate purposes. The private placement was supported by Vivoryon’s longstanding investor Claus Christiansen and KKR Dawn Aggregator L.P., a platform controlled by affiliates of Kohlberg Kravis Roberts & Co. L.P., a leading global investment firm, as new investor to the Company. On October 5, 2022, KKR Dawn Aggregator L.P. notified the Company that it had transferred and novated all of its rights and obligations under the investment agreement to its affiliate Memory Investments S.à r.l.
Financial Results for the Third Quarter of 2022

The Company generated no license revenues or other revenues in the nine months ended September 30, 2022. In the nine months ended September 30, 2021, the Company generated license revenues of EUR 10.8 million from a strategic regional licensing partnership in China.

Research and development expenses increased by EUR 2.5 million to EUR 16.1 million in the nine months ended September 30, 2022, compared to the nine months ended September 30, 2021. This increase is primarily attributable to EUR 1.9 million higher expenses related to our clinical trial VIVIAD, which has advanced significantly compared to the nine months ended September 30, 2021.

General and administrative expenses for the nine months ended September 30, 2022 have increased by EUR 1.0 million to EUR 4.2 million, compared to the nine months ended September 30, 2021. The main reason for that development were higher expenses for share based payments with EUR 1.0 million following new share option grants in 2022.

Net loss for the nine months ended September 30, 2022 was EUR 18.9 million, compared to EUR 7.3 million for the nine months ended September 30, 2021. The difference is mainly due to the strategic regional licensing partnership in 2021, which resulted in a gross profit of EUR 9.2 million (nil in 2022). The Company held EUR 19.8 million in cash and cash equivalents as of September 30, 2022, compared to EUR 14.7 million as of December 31, 2021.

Cash flows provided from financing activities were EUR 19.1 million for the nine months ended September 30, 2022 compared to cash used in financing activities of EUR 0.1 million in the nine months ended September 30, 2021. The change mainly relates to a private placement on April 1, 2022 by way of accelerated book building, placing 2,000,000 registered shares at an offering price of EUR 10.50 per share. The Company’s issued share capital has increased to EUR 22,050,482. The gross proceeds of the offering amounted to EUR 21.0 million. The proceeds of the private placement entered into on September 30, 2022 are not included in cash flows provided from financing activities for the nine months ended September 30, 2022.

Financial Guidance

According to current planning and estimates, Vivoryon expects that its existing cash and cash equivalents will be sufficient to fund its research and development expenses as well as the general and administrative expenses and cash flows from investing and financing activities at least through December 2023. This does not include the exercise of the option to acquire up to an additional 2.054.796 shares for a period ending the later of twelve months after the date of the approval of an EU Recovery Prospectus or the achievement date of a defined clinical milestone.

Conference Call and Webcast

Vivoryon will host a conference call and webcast today, November 22, 2022, at 3:00 pm CET (9:00 am ET). A Q&A session will follow the presentation of the third quarter results and operational progress.

A live webcast and slides will be made available at: www.vivoryon.com/investors-news/news-and-events/presentations-webcasts/

Approximately one day after the call, a slide-synchronized audio replay of the conference will be available on: www.vivoryon.com/investors-news/news-and-events/presentations-webcasts/

On November 22, 2022 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that it will host a webcast and conference call on November 28, 2022, at 4:30 p.m. ET to discuss its financial results for the 2022 fiscal year ended September 30, 2022 (Press release, Arrowhead Pharmaceuticals, NOV 22, 2022, View Source [SID1234624105]).

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Webcast and Conference Call and Details

Investors may access a live audio webcast on the Company’s website at View Source A replay of the webcast will be available approximately two hours after the conclusion of the call.

For analysts that wish to participate in the conference call, please register at https://register.vevent.com/register/BI9d277550044a4f44bfc335d52e38d268. Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call.