On May 16, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported its financial results for the quarter ended March 31, 2022 and provided a clinical update of its anti-cancer drug candidates currently in development for the treatment of primary and metastatic brain and CNS cancer (Press release, CNS Pharmaceuticals, MAY 16, 2022, View Source [SID1234614643]).

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"Since the start of 2022, we have significantly expanded our international presence with clinical approvals in Spain, France and Switzerland received for our potentially pivotal study of Berubicin for the treatment of GBM. Once again our team demonstrated its operational, clinical and regulatory expertise this quarter. These efforts enable us to continue building momentum with patient enrollment – the cornerstone of any successful drug development program. The unmet need in GBM is enormous and knows no geographic borders and this critically important and state of the art trial will, most importantly, advance a much needed potential treatment option to patients. We have been and remain laser focused on executing on all of our operational efforts and look forward to an exciting year ahead," commented John Climaco, CEO of CNS Pharmaceuticals.

Clinical Programs Update

Berubicin – Novel anthracycline

CNS’ lead product candidate, Berubicin, is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier. Berubicin is currently being evaluated in a potentially pivotal global study evaluating its efficacy and safety in the treatment of GBM. The potentially pivotal global trial is an adaptive, multicenter, open-label, randomized and controlled study in adult patients with recurrent glioblastoma multiforme (WHO Grade IV) after failure of standard first-line therapy. Approximately 243 patients with GBM after failure of standard first line therapy will be randomized in a 2:1 ratio to receive Berubicin or lomustine for the evaluation of Overall Survival, the primary endpoint of the study. Overall Survival is a rigorous endpoint that the U.S. Food and Drug Administration (FDA) has recognized as a basis for approval of oncology drugs when a statistically significant improvement can be shown relative to a randomized control arm.

A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months. This review will include additional evaluation of safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.

The FDA recently granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with the FDA to expedite the development and review process. As previously announced, the Company also received Orphan Drug Designation from the FDA which may provide seven years of marketing exclusivity upon approval of an NDA.

For more information about the potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

Upcoming Milestones

Continue to expand potentially pivotal study to evaluate efficacy of Berubicin in the treatment of adult GBM into additional countries;
Interim analysis of the trial when 30-50% of the total expected patients have been on study for 6 months (expected during first half of 2023); and
Complete enrollment in potentially pivotal clinical trial for GBM.
WP1244 Portfolio – Novel class of DNA-binding agents

The Company continues to advance the development of its WP1244 drug technology portfolio, which utilizes anthracycline and distamycin-based scaffolds to create small molecule agents and is believed to be 500x more potent than daunorubicin in inhibiting tumor cell proliferation. Preclinical studies of WP1244 demonstrated high uptake in the brain with antitumor activity. The Company’s development work has produced a new mesylate salt of WP1244, now identified as WP1874. The enhanced solubility of this salt may increase its ability to be formulated for use in an IV infusion, while maintaining similar potency and toxicity characteristics. Going forward, WP1874 will be the primary focus in our development efforts of the WP1244 portfolio. CNS Pharmaceuticals is also evaluating the use of WP1244/WP1874 in the treatment of other primary brain and central nervous system cancers, as well as cancers metastatic to the brain including pancreatic, ovarian, and lymphomas.

Upcoming Milestones

File IND in 2023.
Summary of Financial Results for the First Quarter 2022

The net loss for the three months ended March 31, 2022 was approximately $2.8 million compared to approximately $3.6 million for the comparable period in 2021. The change in net loss is primarily attributable to increased drug manufacturing activities in 2021 in preparation for the commencement of the Company’s clinical trials as well as the timing of annual employee incentive compensation, partially offset by an increase in contract research organization expenses as we are now actively conducting the trial of Berubicin.

The Company reported Research and development expenses of $1.5 million for the three months ended March 31, 2022 compared to approximately $2.2 million for the comparable period in 2021. The change in net loss is primarily attributable to increased drug manufacturing activities in 2021 in preparation for the commencement of the Company’s clinical trials, as well as by the payment of annual employee incentive compensation during the three months ended March 31, 2021 and not having been paid by March 31, 2022, offset by an increase in expenses during the three months ended March 31, 2022 related to contract research organization (CRO) activites in conducting our trial of Berubicin.

General and administrative expense was approximately $1.3 million for the three months ended March 31, 2022 compared to approximately $1.4 million for the comparable period in 2021. This change is primarily due to the payment of annual employee incentive compensation during the three months ended March 31, 2021 and not having been paid by March 31, 2022.

As of March 31, 2022, the Company had cash of approximately $12.4 million and working capital of approximately $13.7 million. In early January 2022, the Company completed an offering of common stock and warrants for gross proceeds of $11.5 million. The Company’s current expectation is that the cash on hand and the proceeds from the offering during January is sufficient to fund our operations into the first quarter of 2023. The timing and costs of clinical trials are difficult to predict and trial plans may change in response to evolving circumstances and as such the foregoing estimates may prove to be inaccurate.

On May 16, 2022 Galectin Therapeutics, Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins, reported financial results and provided a business update for the three months ended March 31, 2022 (Press release, Galectin Therapeutics, MAY 16, 2022, View Source [SID1234614659]). These results are included in the Company’s Quarterly Report on Form 10-Q, which has been filed with the U.S. Securities and Exchange Commission and is available at www.sec.gov.

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Dr. Pol Boudes, Chief Medical Officer, stated: "As we hear more about difficulties of reading and interpreting liver biopsies in pre-cirrhotic NASH, the feedback we get from our investigators reinforces our belief that using the prevention of esophageal varices as our primary outcome of efficacy in NAVIGATE is the appropriate efficacy outcome. Patients that are enrolled in our program have advanced to the cirrhotic stage of NASH and have developed portal hypertension, a severe complication of cirrhosis that impacts their prognosis. This also means that many of our patients have low platelet counts, and because this increases the risk of bleeding, it makes a liver biopsy far too dangerous. These are some of the reasons why we do not believe that biopsies are appropriate for patient selection or endpoints in our target population and is also why we even removed the requirement for baseline biopsies in our NAVIGATE trial. Preventing the development of an esophageal varix, on the other hand, is a very relevant and pragmatic clinical outcome. Unfortunately, too many cirrhotic patients bleed from these varices, and this can be a life-threatening event. Preventing the development of varices eliminates this potentially significant adverse outcome related to cirrhosis. We believe the design of the NAVIGATE study is truly innovative and allows us to move clinical research for liver cirrhosis forward."

Joel Lewis, Chief Executive Officer and President, said: "I am proud of our team and their accomplishments this quarter. Most importantly, as a Company, we achieved an extremely significant milestone. Our previous phase 2 trial, NASH-RX, indicated a favorable safety profile for belapectin over one year of treatment. As of today, due to the length of our adaptively designed phase 2b/3 NAVIGATE trial, our safety profile has been further evaluated by an independent data safety monitoring board who recommended the trial continue as designed. Additionally, our innovative trial design allows trial participants to move directly into the phase 3 treatment course for an additional 18 months. As these and additional patients continue receiving treatment, we continue to expand our data on the safety profile of belapectin. The significance of this safety profile in a severely compromised patient population cannot be overstated.

"We continued to make progress towards our primary goal of completing enrollment in our adaptively designed Phase 2b/3 NAVIGATE trial for the prevention of esophageal varices in patients with NASH cirrhosis. Our strategy to further expand our trial sites in Mexico and Latin America is well underway. We recently conducted a very productive in-person investigator meeting in Mexico where we have added more than 10 new sites. I attended the meeting with my clinical operations staff, and we are extremely enthusiastic about the ability of these sites to quickly enroll patients. I am grateful to all of our investigators and their teams, as well as our consultants in Mexico, for their time and dedication to our trial. Enrollment in the United States continued steadily; however, enrollment in Europe still lags far behind our expectations. We currently expect enrollment to conclude for the Phase 2b portion around the end of the third quarter of this year."

Mr. Lewis continued: "Additionally, we are making progress and are working to compile an Investigational New Drug (IND) package, including the development of a phase 2 trial protocol, with the objective for the Company to file an IND with the FDA oncology division for the treatment of recurrent or metastatic head and neck cancer for belapectin in combination with Keytruda, an immune checkpoint inhibitor. The lack of current treatments for these patients, the low response rates of monotherapy with check-point inhibitors, the limited number of therapies in development, and the resulting very high medical need make this an important area for new combination therapies."

Financial Results

For the three months ended March 31, 2022, the Company reported a net loss applicable to common stockholders of $9.9 million, or ($0.17) per share, compared to a net loss applicable to common stockholders of $6.3 million, or ($0.11) per share for the three months ended March 31, 2021. The increase is largely due to an increase in 2022 research and development expenses related to the Company’s NAVIGATE trial.

Research and development expenses for the three months ended March 31, 2022, was $8.1 million compared with $4.9 million for the three months ended March 31, 2021. The increase was primarily due to costs related to our NAVIGATE clinical trial and other supportive activities. General and administrative expenses for the three months ended March 31, 2022, were $1.9 million, compared to $1.4 million for the three months ended March 31, 2021. The increase was primarily due to non-cash stock-based compensation expense.

As of March 31, 2022, the Company had $31.6 million of cash and cash equivalents. The Company believes it has sufficient cash to fund currently planned operations and research and development activities through at least May 16, 2023.

The Company expects that it will require more cash to fund operations after May 16, 2023, and believes it will be able to obtain additional financing as needed. Currently, we expect to require an additional approximately $40-$45 million to cover costs of the NAVIGATE trial to reach the planned interim analysis estimated to occur in mid-2024, along with drug manufacturing and other research and development activities and general and administrative costs. However, there can be no assurance that we will be successful in obtaining such new financing or, if available, that such financing will be on terms favorable to us.

About Belapectin

Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of NASH and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs, including fibrotic disorders of the liver, lung, kidney, heart and vascular system. Belapectin binds to galectin-3 and disrupts its function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis. A Phase 2 study showed belapectin may prevent the development of esophageal varices in NASH cirrhosis, and these results provide the basis for the conduct of the NAVIGATE trial. The NAVIGATE trial (www.NAVIGATEnash.com), titled "A Seamless Adaptive Phase 2b/3, Double-Blind, Randomized, Placebo-controlled Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis," began enrolling patients in June 2020, and is posted on www.clinicaltrials.gov (NCT04365868). Galectin-3 has a significant role in cancer, and the Company has supported a Phase 1b study in combined immunotherapy of belapectin and KEYTRUDA in advanced melanoma and in head and neck cancer. This trial provided a strong rationale for moving forward into a Company-sponsored Phase 2 development program, which the company is exploring.

About Fatty Liver Disease with Advanced Fibrosis and Cirrhosis

Non-alcoholic steatohepatitis (NASH) has become a common disease of the liver with the rise in obesity and other metabolic diseases. NASH is estimated to affect up to 28 million people in the U.S. It is characterized by the presence of excess fat in the liver along with inflammation and hepatocyte damage (ballooning) in people who consume little or no alcohol. Over time, patients with NASH can develop excessive fibrosis, or scarring of the liver, and ultimately liver cirrhosis. It is estimated that as many as 1 to 2 million individuals in the U.S. will develop cirrhosis as a result of NASH, for which liver transplantation is the only curative treatment available. Approximately 9,000 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis or cirrhosis.

On MAY 16, 2022 CG Oncology, Inc., a clinical-stage biotechnology company focused on developing oncolytic immunotherapies for patients with advanced cancer, reported that interim results from the global Phase 2 study (CORE1) of CG0070 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab), for the treatment of patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) (Press release, CG Oncology, MAY 16, 2022, View Source [SID1234614675]).

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The results (Session MP54-03) were presented at the 2022 American Urological Association (AUA) Annual Meeting. The preliminary data adds to that presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) earlier this year and continues to show both promising early anti-tumor activity and tolerability of CG0070 in combination with pembrolizumab for patients with BCG unresponsive NMIBC.

Summary of Interim Clinical Results

As of the interim analysis, based on a data cutoff on April 28, 2022, 22 patients were evaluable for efficacy with a minimum of 3 months follow up.
91% of patients evaluable for efficacy (n=20/22) have achieved complete response (CR) at the initial 3-month timepoint. Of those patients evaluable for CR at additional timepoints, 87% (n=15) have also maintained a CR through 6 months, 80% (n=10) through 9 months and 75% (n=8) at the 12-month assessment.
Treatment related adverse events were generally limited to transient grade 1-2 local genitourinary symptoms including pollakiuria, bladder spasm, dysuria, fatigue, nocturia, hematuria, chills, and immune-related adverse events including hyperglycemia and hypothyroidism.
About the CORE1 Study

Under a previously announced clinical collaboration with Merck (known as MSD outside the US and Canada) relating to the investigation of CG0070 used in combination with pembrolizumab, the goal of CORE1, which will enroll up to 35 patients, is to evaluate the safety and efficacy of CG0070 plus pembrolizumab for the treatment of NMIBC unresponsive to BCG.

More information about the study can be found at www.clinicaltrials.gov (NCT04387461).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About CG0700

CG0070, a selective oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective retinoblastoma (Rb) pathway. CG0070 was designed to replicate inside tumor cells with dysfunctional Rb pathways, causing tumor cell lysis and immunogenic cell death. The rupture of cancer cells releases tumor-derived antigens and GM-CSF, which stimulates a systemic anti-tumor immune response. In advanced clinical trials, CG0070 is a safe and efficacious agent in NMIBC following BCG failure. CG0070 is currently in late-stage clinical trials across a variety of solid cancers, as a monotherapy or in combination with immune checkpoint inhibitors.

On May 16, 2022 Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company with a Research & Development ("R&D") innovation engine that aims to discover, develop and ultimately deliver impactful medicines to patients, reported financial results for the first quarter ended March 31, 2022 and provided business updates (Press release, Centessa Pharmaceuticals, MAY 16, 2022, View Source [SID1234614702]).

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"We continue to execute against our focused strategy and advance our pipeline of innovative, high impact rare disease and immuno-oncology assets that we believe will position Centessa for multiple value-creating milestones through our extended cash runway. Our model is focused on judicious capital and resource allocation decisions which, combined with our strong balance sheet, provide us with significant optionality to meet our ‘4×24’ goal of four registrational programs in 2024," said Saurabh Saha, MD, PhD, Chief Executive Officer of Centessa. "Our most advanced program, lixivaptan for ADPKD, continues to progress in the ongoing registrational ACTION Study. In addition, ZF874 for AATD is on track for data later this year from the ongoing Phase 1 study, we continue to anticipate SerpinPC in Hemophilia to enter registrational trials this year, and we recently commenced dosing in the Phase 1 study of CBS001, an anti-LIGHT monoclonal antibody. In the near term, we are excited to share initial preclinical data for LB101, our PD-L1xCD47 LockBody at ASCO (Free ASCO Whitepaper) 2022 in June."

First Quarter 2022 Highlights and Recent Business Updates
Clinical Development Programs:
•SerpinPC: Based on the FDA feedback received in the first quarter of 2022, the Company is proceeding with a streamlined, integrated registrational development plan initially for Hemophilia B (with and without inhibitors).
•Lixivaptan: Commenced dosing in the pivotal Phase 3 clinical trial ("ACTION Study") evaluating lixivaptan as a potential treatment for ADPKD. In addition, a key US patent was issued on

February 8, 2022, which covers the use of lixivaptan for the treatment of ADPKD. The patent term expires June 8, 2038, before considering possible patent term extensions or adjustments.
•CBS001 in inflammatory / fibrotic diseases: Commenced dosing of healthy volunteers in a Phase 1 study of CBS001, a high affinity anti-LIGHT monoclonal antibody.

Business Highlights:
•During the first quarter of 2022, the Company named Antoine Yver, MD, MSc, Executive Vice President and Chairman of Development; Javad Shahidi, MD, MSc, Chief Medical Officer; and Josh Hamermesh, MBA, Senior Vice President, Business Development.
•In March 2022, the Company announced ‘4×24’, its corporate goal to have four registrational programs in 2024.
•In March 2022, the Company announced plans to discontinue the small molecule EGFR inhibitor discovery programs (PearlRiver Bio) and the dual-STAT3/5 degrader program (Janpix Limited) and is now winding down operations at both subsidiaries. The Company also continues to evaluate strategic options, including potential divestment, for imgatuzumab (Pega-One).
•In February 2022, dosing of the first patient with lixivaptan in the Phase 3 ACTION Study triggered settlement of the contingent value rights ("CVRs") originally issued to the former shareholders and option holders of Palladio Biosciences in connection with its acquisition by Centessa in January 2021.

Anticipated Upcoming Program Milestones
•LB101 in Solid Tumors: Preclinical data for LB101, a PD-L1xCD47 LockBody, will be presented in a poster at ASCO (Free ASCO Whitepaper) 2022 on June 5, 2022. An IND for LB101 is planned for late 2022.
•ZF874 in Alpha-1 Antitrypsin Deficiency (AATD): The Company expects to share data from the ongoing Phase 1 study in the second half of 2022. This interim data will include multiple dose cohorts with PiMZ and PiZZ subjects.
•SerpinPC in Hemophilia: In the second half of 2022, the Company expects to initiate a streamlined clinical program to support registration for SerpinPC for the treatment of Hemophilia B (with and without inhibitors). Additionally, the Company expects to report data from the Phase 2a open label extension study in the fourth quarter of 2022 for the 48-week flat dose portion and the 24-week high dose portion (1.2mg/kg every two weeks). This is anticipated to provide two years of safety and efficacy data across multiple dose levels.
•CBS004 in Autoimmune Diseases: IND is planned for late 2022.

First Quarter 2022 Financial Results
•Cash and Cash Equivalents: $544.5 million as of March 31, 2022 which the Company expects will fund operations to mid-2024, without drawing on the remaining available tranches under the Oberland credit facility.

•Research & Development Expenses: $36.9 million for the quarter ended March 31, 2022 compared to $10.1 million for the period from January 30, 2021 through March 31, 2021.
•General & Administrative Expenses: $14.4 million for the quarter ended March 31, 2022 compared to $5.6 million the period from January 30, 2021 through March 31, 2021.
•Net Loss Attributable to Ordinary Shareholders: $54.5 million for the quarter ended March 31, 2022 compared to $238.7 million for the period from January 30, 2021 through March 31, 2021 (which includes a special non-cash $220.5 million charge for acquired in-process R&D associated with the Centessa subsidiary acquisitions).

On May 16, 2022 Nykode Therapeutics reported that (Press release, Nykode Therapeutics, MAY 16, 2022, View Source [SID1234614573])

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Highlights:
• Nykode announced completion of patient enrollment in its Phase II trial of VB10.16 in combination with immune checkpoint inhibitor atezolizumab for the treatment of advanced cervical cancer
• Received milestone payment of USD 20 million for initiation of phase 1b trial Highlights after March 31st, 2022:
• Nykode Therapeutics announced positive interim results from its Phase II trial with VB10.16 in combination with atezolizumab in advanced cervical cancer o Anti-tumor activity of VB10.16 in combination with atezolizumab was observed in a heavily pretreated population of patients with HPV16-positive advanced cervical cancer. Strong overall response rate (ORR) was observed in both PD-L1 positive patients (ORR of 27%) and in PD-L1 negative patients (ORR of 17%). Overall ORR of 21% including two complete responses (CRs) and six partial responses (PRs) were observed in the 39 patients studied o VB10.16 in combination with atezolizumab demonstrated a very high disease control rate (DCR, which includes patients who have achieved complete response, partial response and stable disease) of 64% (77% in PD-L1 positive patients and 58% in PD-L1 negative patients)
• Nykode Therapeutics presented preclinical data from its second generation Vaccibody vaccine technology at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting
• At Nykode’s AGM on May 12, 2022, it was resolved to convert the Company from a private limited liability company (AS) to a public limited liability company (ASA)
• Elaine Sullivan and Anne Whitaker elected to join the Board of Directors at the Company’s AGM on May 12, 2022 Michael Engsig, Chief Executive Officer at Nykode, comments: "I am delighted that the interim results from the phase II study with VB10.16 in combination with atezolizumab in HPV-16 positive cervical cancer support Nykode’s unique approach of targeting Antigen Presenting Cells (APCs), designed to produce a robust and long-lasting CD8 killer T cell response against cancer cells. In particular I am excited about the signs of durable anti-tumor activity in a heavily pre-treated and hard to treat population of patients with late-stage HPV16-positive cervical cancer.

Furthermore, the indication that the treatment may benefit not only PD-L1 positive patients but also PD-L1 negative patients and patients with immune excluded tumors may bode well for the continued development." Michael Engsig continues "Building on the promising clinical efficacy and favorable safety profile that was observed with VB10.16, Nykode has started planning the NYK003-C-03 Phase 1b trial of VB10.16 in combination with a check point inhibitor in patients with HPV16-positive squamous cell head and neck cancer (HNSCC). The trial is expected to start in the second half of 2022. In addition to the positive development of the wholly owned pipeline, and the disclosure of exciting new preclinical data from our second generation Vaccibody technology platform, I am pleased to report that the Regeneron collaboration is off to a good start. It is progressing according to plan, with lots of energy and good discussions."R&D update Nykode’s modular technology platform is very versatile and may be adapted to generate the desired immune response profile. Hence, Nykode’s platform may be applied across a broad range of immunotherapy areas as innovative solutions to an unmet medical need. Nykode continues to increase the headcount across all functions including R&D to continue to build competencies and support the strategy execution. Please find below an update on Nykode’s current research and development activities.

Oncology VB10.16 VB10.16 is a therapeutic HPV vaccine directed against HPV16+ induced malignancies:
• Clinical trial VB C-02: − Clinical stage: Phase II − Cancer indication: HPV16+ advanced, non-resectable cervical cancer − Fully enrolled − ClinicalTrials.gov Identifier: NCT04405349 Status and highlights The trial is fully enrolled and reported positive interim efficacy and safety data on May 9, 2022. Interim results from 39 patients with a median follow up of 6 months show an ORR of 21%, including two patients who achieved a complete response and six who achieved a partial response, and a very high disease control rate of 64%. The trial enrolled a heavily pre-treated patient population with more than two thirds of the patients having received at least two previous systemic lines of treatment. Interestingly, anti-tumor activity was observed in both PD-L1 positive (ORR of 27% and DCR of 77%) and PD-L1 negative patients (ORR of 17% and DCR of 58%) indicating a potential clinical benefit also in the PD-L1 negative population. In addition, a DCR of 71% was observed in patients with noninflamed tumors, including both immune desert and T cell excluded tumors.

Together these findings suggest a differentiated anti-tumor response pattern of the combination treatment compared to checkpoint inhibitor monotherapy. Nykode expects to report updated efficacy data read-outs from VB C-02 during the first half of 2023. VB10.NEO VB10.NEO is an individualized neoantigen cancer vaccine, exclusively licensed to Genentech:
• Clinical trial VB N-01: − Clinical stage: Phase I/IIa − Cancer indications: Melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN) − Fully enrolled − ClinicalTrials.gov Identifier: NCT03548467
• Clinical trial VB N-02: − Clinical stage: Phase Ib − Cancer indications: Locally advanced and metastatic tumors − ClinicalTrials.gov Identifier: NCT05018273 Org.no. N-990 646 066 MVA 5 Status and highlights News flow updates relating to VB10.NEO are in general at Genentech’s discretion. Recruiting sites are open in US, Germany and Spain. Infectious Diseases Nykode’s infectious disease initiative continues to generate supportive data and explore and evaluate a diverse set of pathogens as potential next future clinical vaccine targets. VB10.COV2 Nykode has chosen a 2-arm strategy for its VB10.COV2 project to fight SARS-CoV2 variants of concern (VoC*).

VB10.2129 (RBD candidate) and VB10.2210 (T cell candidate) are two vaccines designed using Nykode’s modular and APC targeted technology:
• Clinical trial VB-D-01, investigating the two vaccine candidates, VB2129 and VB2210. − Clinical stage: Phase I/II − Pathogen: SARS CoV-2 − ClinicalTrials.gov Identifier: NCT05069623 VB10.2129 – 2nd generation vaccine addressing novel variants of concern* VB10.2129 contains the RBD domain of the Beta variant of concern B1.351. Importantly, preclinical data demonstrate induction of rapid, strong and persistent neutralizing antibody responses in animal models by VB2129 not only against the Beta variant, but also across several other major variants of concern. Nykode’s RBD vaccine candidate has the potential to induce rapid and strong levels of neutralizing antibody responses addressing both existing and emerging variants of concern.

VB10.2210 – 3rd generation universal broadly protective T cell vaccine Increasing evidence highlights the importance of broad T cell responses in providing rapid as well as long-term memory responses against COVID-19 with limited sensitivity to viral mutations. The vaccine includes SARS-CoV2 T cell epitopes identified and validated by Adaptive Biotechnologies. Nykode aims to boost and broaden the most clinically relevant and conserved T cell responses against a broad set of SARS-CoV-2 epitopes identified by Adaptive Biotechnologies. Preclinical data confirm induction of strong T cell responses against multiple SARS-CoV2 antigens in several mouse models. The aim is to induce long-lasting protective immunity across all population groups and across current and future variants. VB-D-01 trial The VB-D-01 trial is a Phase I/II, open label, dose escalation trial to determine safety and immunogenicity of two SARS CoV-2 vaccine candidates VB10.2129 and VB10.2210. Status and highlights VB10.2129 (RBD candidate): First subject dosed November 3, 2021.

The trial is fully enrolled at two out of three dose levels in the dose-escalation cohort. VB10.2210 (T cell candidate): First subject dosed December 27, 2021. The trial is fully enrolled at all three dose levels in the dose-escalation cohort. Results from the Phase I dose-escalation cohort is expected during the second half of 2022.

*Note: All viruses, including SARS-CoV-2, mutate and change over time. Most changes have limited impact on the virus’ properties. However, some changes may affect the virus’s properties, e.g., as how easily it spreads, the associated disease severity, or the performance of vaccines, diagnostic tools and so forth. The emergence of variants that poses an increased risk to global public health has prompted the characterization of specific variants of concern, in order to prioritize global monitoring and research, and ultimately to inform the ongoing response to the COVID19 pandemic. Source: Tracking SARS-CoV-2 variants (who.int)

MVA 6 Autoimmune disorders Autoimmune disorders are caused by unwanted immunogenicity to autoantigens. Antigen-specific tolerization for the treatment of auto-immune diseases has the potential to blunt autoimmunity without compromising normal immune function. Nykode is exploring autoimmunity model systems to generate pre-clinical proof-of-concept for the ability to induce meaningful antigen-specific immune tolerance. Nykode has demonstrated that its exploratory tolerizing vaccines induce proliferation of epitope specific T regulatory cells in such model systems and will continue its research and know-how building in the area. Other Uplift on Oslo Stock Exchange Nykode has initiated a process for transfer of the listing of its shares from Euronext Growth to the main market of the Oslo Stock Exchange. The expected timing is end of the second quarter of 2022.

Financial review Income statement The net result for the first quarter of 2022 was a net loss of USD 6.9 million compared to a net loss of USD 6.5 million in the first quarter of 2021. The change in net loss was mainly due to increased activities and operations in Nykode, leading to increased operating expenses and employee benefit expenses. This was offset by an increase in total revenue as well as a decrease in the social security cost accrual related to share-based payments included under employee benefit expenses. Revenue and other income Total revenue and other income amounted to USD 1.0 million in the first quarter of 2022 (Q1 2021: USD 0.8 million).

The increase was mainly due to increased R&D service activities under the agreements with Genentech and Regeneron. Operating expenses Total operating expenses amounted to USD 9.6 million in the first quarter of 2022 (Q1 2021: USD 8.3 million). Employee benefit expenses were USD 1.3 million in the first quarter (Q1 2021: USD 3.9 million). The decrease in employee benefit expenses in 2022 is primarily due to the reduction of the social security cost accrual related to share-based payments. This accrual is dependent on the share price as Nykode is required to accrue for the social security cost for all warrants and options that are in-the-money at the balance sheet date. This relates to both the current and the non-current portion. As the share price decreased during the quarter the accrual is also reduced. The corresponding reduction is USD 4.8 million.

The decrease is offset by the planned increase in headcount. Other operating expenses increased from USD 4.3 million in the first quarter of 2021 to USD 7.9 million in the first quarter of 2022, driven by increased operating activity. Net financial income and expenses Net financial income and expenses were USD 0.1 million in the first quarter of 2022 (Q1 2021: USD 0.8 million loss). Finance income and finance costs mainly relate to movements in foreign currency exchange rates and fair value adjustments of financial instruments. Income tax expenses The Group recognized tax income of USD 1.7 million in the first quarter of 2022 and USD 1.7 million in the first quarter of 2021.

The income tax expense is primarily related to movement in deferred tax. Statement of financial position Cash At March 31, 2022, Nykode had a cash position of USD 225.7 million compared to USD 216.2 million at December 31, 2021. The increase in cash is mainly a result from operating activities. Equity At March 31, 2022, total equity amounted to USD 188.6 million, compared to USD 194.1 million at December 31, 2021. The change mainly reflects the net loss of the period of USD 6.9 million, the exercise of warrants and options and recognition of share-based payments. Trade receivables At March 31, 2022, trade receivables amounted to USD 2.5 million, compared to USD 23.8 million at December 31, 2021. The decrease is mainly due to the receipt of the USD 20 million milestone payment from Genentech in the first quarter of 2022.

Trade and other payables At March 31, 2022, trade and other payables amounted to USD 7.0 million, compared to USD 8.5 million at December 31, 2021. Contract liability At March 31, 2022, total contract liability amounted to USD 18.0 million, compared to a contract liability of USD 16.0 million at December 31, 2021. The contract liability is mainly due to timing of invoicing to Genentech as well as recognition of the service component under the Genentech agreement. Other current financial assets At March 31, 2022, total other current financial assets amounted to USD 12.2 million compared to USD 12.2 million at December 31, 2021. Cash flow Net change in cash and cash equivalents was positive USD 9.5 million in the first quarter of 2022 (Q1 2021: USD 4.1 million negative).

Cash and cash equivalents increased to USD 225.7 million at the end of the period, compared to USD 179.7 million at the end of the same period in 2021. Cash flow from operating activities Net cash flow from operating activities was positive USD 10.9 million in the first quarter of 2022 (Q1 2021: USD 5.0 million negative). This was primarily driven by the decrease in trade receivables due to the receipt of the milestone payment from Genentech, offset by a negative profit before tax. Cash flow from investing activities Cash flow from investing activities was negative USD 1.6 million in the first quarter of 2022 (Q1 2021: USD 0.6 million positive).

The amounts mainly relate to the purchase of property, plant and equipment. Cash flow from financing activities Cash flow from financing activities was positive USD 0.1 million in the first quarter of 2022 (Q1 2021: USD 0.3 million positive). The amounts primarily relate to the proceeds from equity issuance, offset by payment of lease liabilities. Outlook The first major clinical objective for 2022 has been reached, namely:-VB C-02 clinical trial, positive interim efficacy and safety results have been reported Expected outlook and news flow regarding Nykode’s key priorities for the remainder of 2022 include: Uplift from Euronext Growth to the main list of Oslo Stock Exchange VB10.16 – Initiation of NYK003-C-03 Phase Ib trial in HNSCC VB-D-01 trial – Phase I key results with Nykode’s two COVID vaccine candidates measuring T cell and antibody responses Update on manufacturing strategy The Company has a strong cash position and no debt.

The Company is in continuous dialogue with academic and industrial entities and will announce new key collaborations and partnerships if or when they may occur. The COVID-19 pandemic and the situation in Ukraine may impact timelines and operations.

Disclaimer This announcement and any materials distributed in connection with this announcement may contain certain forward-looking statements. By their nature, forward-looking statements involve risk and uncertainty because they reflect the company’s current expectations and assumptions as to future events and circumstances that may not prove accurate. A number of material factors could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements.