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Redx Presents Encouraging Phase 1 Data at ESMO for its Porcupine Inhibitor RXC004 in Patients with Advanced Solid Tumours

On September 20, 2021 Redx Pharma (AIM: REDX), the drug discovery and development company focused on cancer and fibrosis, reported data from the monotherapy module of its Phase 1 clinical study of RXC004 for the first time (Press release, Redx Pharma, SEP 20, 2021, View Source [SID1234588078]). The data was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 by the study’s lead investigator, Dr Natalie Cook, from the University of Manchester and Christie NHS Foundation Trust.

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The Phase 1 trial (clinicaltrials.gov NCT03447470) is evaluating RXC004, a wholly owned small-molecule Porcupine inhibitor as a monotherapy (Module 1) and in combination with nivolumab (Module 2) in unselected patients with advanced solid tumours for whom no standard therapy is available. The primary objective of the open label, ‘3+3’ dose escalation Phase 1 study is to assess the safety and tolerability of RXC004 with secondary endpoints including pharmacokinetics (PK) and anti-tumour activity, as measured by Response Evaluation Criteria in Solid Tumours (RECIST 1.1). The data presented are from 25 patients in the completed monotherapy module of the trial and informed the selection of 2mg as the dose for the planned Phase 2 monotherapy trials testing RXC004 in three different Wnt-ligand dependent cancers.

D r Natalie Cook, Lead Investigator of the Study, from the University of Manchester and Christie NHS Trust, commented: "This Phase 1 study provides encouraging evidence of the potential of Porcupine inhibition as a targeted treatment approach and supports the progression of RXC004 into Phase 2 development in selected patients with Wnt-ligand driven cancers." Lisa Anson, Chief Executive Officer of Redx Pharma, added: "The first clinical data on our Porcupine inhibitor, presented at the prestigious ESMO (Free ESMO Whitepaper) Congress, illustrate RXC004’s potential to improve outcomes in patients with Wnt-ligand driven advanced solid tumours who have limited treatment options. RXC004 demonstrated a well-tolerated profile at the selected dose and showed differentiated signs of efficacy in Wnt-ligand dependent tumours. We are excited to move to Phase 2 later this year, with a larger number of patients with Wnt-ligand driven cancers, who represent those most likely to benefit from treatment with RXC004."

Key results presented at ESMO (Free ESMO Whitepaper) highlighted:
· RXC004 was safe and well tolerated as a single agent at doses up to 2mg. No grade 4 or 5 adverse events (AEs) were reported at these dose levels and the most common treatment-related AEs across all patients were fatigue (52% of patients), nausea (44%), decreased appetite (40%), dysgeusia (‘altered taste’) (40%) and vomiting (24%). RXC004, given at doses up to 2mg alongside denosumab prophylaxis, averted the bone toxicity traditionally associated with Wnt-pathway inhibition, as evidenced by the absence of both increases in the bone turnover marker βCTX and spontaneous fractures.
· An oral dose of 2mg once daily is selected as the Phase 2 dose of RXC004 in monotherapy. The 2mg once-daily dose demonstrated high plasma exposure levels, while minimising adverse events. RXC004 exposures were dose proportional and median half-life was 14.5 hours. In addition, the pharmacodynamic marker of Axin-2 levels in skin showed active target engagement. · Efficacy data supports further investigation of RXC004 use in Wnt-ligand dependent tumours.

Although the study was not designed to assess efficacy as a primary endpoint, 18 patients had RECIST-evaluable disease. Of these patients: o 7 patients had Wnt-ligand dependent tumours, defined as those having detectable ring-finger protein 43 (RNF43) Loss of Function or R-spondin (RSPO) fusion, biliary-tract cancers or thymus cancers; 6 patients had Wnt-ligand independent tumours, defined as those having no detectable RNF43 Loss of Function or RSPO fusion, or colorectal tumours with detectable downstream adenomatous polyposis coli (APC) mutations; 5 patients were of unknown Wnt-ligand status. o At the data cut-off date on 30 July 2021, 5 of 7 patients (71%) with Wnt-ligand dependent tumours had durable RECIST stable disease (SD) versus 0 of 11 (0%) patients with independent or unknown Wnt-ligand status. o Median treatment duration was 13.1 weeks (6.4-25.4 weeks) for patients with Wnt-ligand dependent tumours versus 6.6 weeks (5.4-7.3 weeks) for patients with either Wnt-ligand independent tumours or tumours of unknown Wnt-ligand status.

The results from the second module in the Phase 1 study testing RXC004 in combination with nivolumab (OPDIVO-Bristol Myers Squibb, an anti-PD-1 antibody) are expected in H2 2021 and will be used to define a dose of RXC004 to be used in combination with standard dose nivolumab in a Phase 2 study in patients with genetically selected MSS mCRC. A link to the presentation can be found here: View Source Redx to host R&D Event Today’s data will be discussed by Medical Experts during Redx’s online R&D Event to be held on Monday 11 October 2021 at 1:00pm BST / 8.00am EDT. The event will also cover the Company’s pipeline beyond RXC004. To register for the event, please email [email protected] About the Phase 2 programme for RXC004 Redx plans to commence a global Phase 2 monotherapy programme in three tumour types to assess RXC004 efficacy in patients with Wnt-ligand driven cancers. For patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) only those with RNF43 mutations or RSPO fusions will be enrolled. For pancreatic cancer patients only those with RNF43 mutations will be enrolled. The third tumour type to be studied will be biliary-tract cancer, a tumour known to have high Wnt-ligand dependency which will enrol unselected patients. All three of these cancer types have high unmet need with limited treatment options and poor 5-year survival rates of less than 3% for biliary and pancreatic cancer and 14% for MSS mCRC. All three studies are planned to commence in H2 2021 and initial results are expected in 2022.

About RXC004
RXC004 is a wholly owned, potent, selective, oral, small-molecule inhibitor of the Porcupine enzyme, a key activator of Wnt ligands in the Wnt-signalling pathway. The Wnt pathway is well established as a driver of both tumour growth and immune evasion. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which has also been linked to resistance to immune-checkpoint inhibitors (ICIs) such as nivolumab. By selecting patients with tumours that have high Wnt-ligand dependency, such as tumours with mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to allow the patient’s immune system to better recognise and attack the tumour. ICIs such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt-pathway activation can enhance the ability of the tumour to evade destruction by the immune system and has been linked to lack of response to ICIs in these tumours. Redx scientists have demonstrated preclinically that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential as a monotherapy or combination therapy with ICIs.

PDS Biotech Achieves Safety Requirement Milestone For the First 12 Patients in the VERSATILE-002 Phase 2 Combination Trial of PDS0101-KEYTRUDA® in Advanced Head and Neck Cancer

On September 20, 2021 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies based on the Company’s proprietary Versamune T-cell activating technology, reported its VERSATILE-002 Phase 2 study for the treatment of advanced human papillomavirus (HPV16)-associated head and neck cancer achieved its preliminary safety benchmark in its first 12 patients (Press release, PDS Biotechnology, SEP 20, 2021, View Source [SID1234588076]). Enrollment in the trial, which studies PDS0101 administered in combination with KEYTRUDA (pembrolizumab), will now continue to full enrollment of the first stage of the study, which will assess efficacy in 17 checkpoint inhibitor (CPI) naïve patients and in an additional group of 21 patients who have also failed prior therapy with checkpoint inhibitors (CPI refractory). The trial is being conducted in collaboration with Merck & Co.

VERSATILE-002 is studying two groups of HPV16-positive head and neck cancer patients whose cancer has returned or spread. The first group has not been previously treated with a checkpoint inhibitor (CPI naïve). The second group of patients have failed multiple treatments including CPI therapy (CPI refractory). As specified in the clinical trial design, the achievement of an objective response as measured by radiographic tumor responses according to RECIST 1.1 (tumor reduction of 30% or more) among at least four of the first 17 patients in the CPI naïve arm and at least 2 patients in the first 21 patients of the CPI refractory arm will trigger advancement to the second stage of the study and full enrollment of the planned 95 patients.

"The achievement of this important milestone in the VERSATILE-002 Phase 2 clinical trial strengthens the evidence regarding the safety of PDS0101. Treatment-related adverse events (TRAEs) generally appear to be limited to transient, manageable local injection site reactions," commented Dr. Lauren V. Wood, Chief Medical Officer of PDS Biotech. "There is an enormous unmet medical need for more effective treatment of advanced head and neck cancer. We believe the combination of PDS0101 and KEYTRUDA has the potential to significantly improve clinical outcomes for these patients who have limited treatment options. We look forward to continuing to share data from this trial as they become available."

Dr. Jared Weiss, Section Chief of Thoracic and Head and Neck Oncology at the University of Carolina at Chapel Hill School of Medicine and Lineberger Comprehensive Cancer Center, is serving as the Lead Principal Investigator of VERSATILE-002. Patients interested in enrolling in this clinical study should email [email protected] or visit the website at View Source to learn more.

The advancement of the VERSATILE-002 trial follows the previously disclosed presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting of interim data in a separate Phase 2 trial (NCT04287868) being led by the National Cancer Institute (NCI). That trial is evaluating the combination of PDS0101 with two investigational immunotherapies in patients with advanced HPV-related cancers. That trial has enrolled patients with anal, cervical, head and neck, vaginal and vulvar cancer, who have failed prior treatment. Objective responses measured according to RECIST 1.1 (tumor reduction of 30% or more) were reported in 83% (5/6) of HPV16-positive patients who had failed chemotherapy and radiation but were CPI naive. In CPI refractory patients, tumor reduction was reported in 58% (7/12) and objective responses in 42% (5/12). Two patients, one in each group were reported to have a complete response (no evidence of disease) at the time of reporting. Clinical responses were observed in all HPV16-positive tumor types enrolled. More information on this study can be found on PDS Biotech’s website.

Entry into a Material Definitive Agreement

On September 20, 2021, Lixte Biotechnology Holdings, Inc. ("we," "our" or the "Company") reported that it entered into an at-the-market sales agreement (the "Sales Agreement") with WestPark Capital, Inc. (the "Agent") pursuant to which we may offer and sell from time to time through the Agent, acting as agent, shares of our common stock, $0.0001 par value per share, having an aggregate offering price of up to $10,000,000, subject to the terms and conditions of the Agreement (Filing, 8-K, Lixte Biotechnology, SEP 20, 2021, View Source [SID1234588075]). The issuance and sale, if any, of shares of common stock through the Agent under the Sales Agreement will be will be made pursuant to the Company’s effective shelf registration statement on Form S-3 (File No. 333-252430) (the "Registration Statement") filed with the Securities and Exchange Commission, or "SEC," on January 26, 2021, and declared effective on February 5, 2021, and are described in detail in the related base prospectus, dated February 5, 2021 and prospectus supplement, dated September 20, 2021, included as part of our Registration Statement.

Under the sales agreement, the Agent may sell shares of our common stock by any method permitted by law deemed to be an "at-the-market" offering as defined in Rule 415 of the Securities Act of 1933, as amended, including, but not limited to, sales made directly on the Nasdaq Capital Market, on any other existing trading market for our common stock or to or through a market maker other than on an exchange or otherwise, in negotiated transactions at market prices prevailing at the time of sale or at prices related to such prevailing market prices, and/or any other method permitted by law. The Agent has agreed in the sales agreement to use its commercially reasonable efforts consistent with its respective normal trading and sales practices to sell shares in accordance with our instructions (including any price, time or size limit or other customary parameters or conditions we may impose). Actual sales will depend on a variety of factors to be determined by the Company from time to time, including (among others) market conditions, the trading price of the Company’s common stock, capital needs and determinations by the Company of the appropriate sources of funding for the Company. The Company is not obligated to make any sales of common stock under the Sales Agreement and the Company cannot provide any assurances that it will issue any shares pursuant to the Sales Agreement.

We have agreed to pay the Agent a commission rate of 2.5% of the gross sales price per share of any of our shares of common stock sold through the Agent under the sales agreement, and have provided the Agent with customary indemnification and contribution rights. In addition, we have agreed to reimburse certain legal expenses and filing fees incurred by the Agent in connection with the offering pursuant to the Sales Agreement, including fees and expenses of the Agent’s legal counsel not to exceed $50,000, plus certain ongoing disbursements of its legal counsel up to $1,250 per calendar quarter.

The offering of shares of our common stock pursuant to the Sales Agreement will terminate upon the earliest of (i) the sale of the maximum dollar amount of shares of common stock subject to the Sales Agreement, (ii) the termination of the Sales Agreement by us or the Agent, and (iii) the expiration of the shelf registration statement on Form S-3 (File No. 333-252430) on the third anniversary of the initial effective date of such registration statement.

A copy of the Sales Agreement is filed as Exhibit 10.1 to this Current Report on Form 8-K (this "Report") and is incorporated herein by reference. The description of the Agreement is qualified in its entirety by reference to Exhibit 10.1 to this Report.

This Report, including the exhibits filed herewith, is not an offer to sell or the solicitation of an offer to buy the shares or any other securities of the Company, nor shall there by any offer, solicitation or sale of the shares or any other securities of the Company in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state.

A copy of the opinion of TroyGould PC relating to the legality of the shares is filed as Exhibit 5.1 to this Report and is filed with reference to, and is hereby incorporated by reference into, the Registration Statement.

Nordic Nanovector ASA – allocation of PSUs

On September 20, 2021 The Board of Directors of Nordic Nanovector ASA ("Nordic Nanovector" or the "Company") reported that it has on 20 September 2021 decided to grant 350,000 Performance Share Units ("PSUs") to the Company’s new CEO and primary insider Mr. Erik Skullerud in accordance with the authorisation granted at the Annual General Meeting held on 28 April 2021 (the "AGM") (Press release, Nordic Nanovector, SEP 20, 2021, View Source;allocation-of-psus-301380251.html [SID1234588073]).

The terms and conditions of the PSUs, which are part of the Company’s long-term incentive plan for employees, are described on pages 25-27 in the Company’s annual report for 2020.

The PSUs are granted without consideration. The PSUs are non-transferable and will vest three years after the date of grant subject to satisfaction of the applicable vesting conditions. Each vested PSU will give the holder the right to acquire one share in the Company at an exercise price corresponding to the par value of the shares being NOK 0.20.

In accordance with the resolution at the AGM, the PSUs are secured by a corresponding number of free-standing warrants. The sole purpose of the warrants is to ensure delivery of shares in the Company upon exercise of the PSUs. The warrants do not give the PSU holders (or the option holders) a right to subscribe for any additional shares in the Company.

Mr. Skullerud will hold 350,000 PSUs and 0 shares after the transaction.

The allocation of PSUs is in accordance with the Board of Director’s declaration on salaries and other remuneration to the senior executive management, as approved by the Company’s AGM.

Primary insider notification pursuant to the Market Abuse Regulation article 19 are attached.

Enveric Biosciences to Participate in Upcoming Investor Conferences in September 2021

On September 20, 2021 Enveric Biosciences (NASDAQ: ENVB) ("Enveric" or the "Company"), a biotechnology company developing a next-generation mental health and oncology treatment clinical discovery platform for the mind and body using psychedelics and cannabinoids, reported that Dr. Joseph Tucker, Chief Executive Officer of Enveric Biosciences, will participate in two upcoming investor conferences (Press release, Enveric Biosciences, SEP 20, 2021, View Source [SID1234588070]):

Maxim’s Advances in Mental Health Virtual Conference
Wednesday, September 22nd at 10:00 a.m. ET
Panel titled: Next Gen Psychedelics: Novel Chemical Entities
To attend, register here

Benzinga’s Healthcare Small Cap Virtual Conference
Thursday, September 30th at 3:40 p.m. ET
To attend, register here

For more information about the conferences, or to schedule a one-on-one meeting with Enveric’s management, please contact your appropriate representative directly, or send an email to Maxim at [email protected], Benzinga at [email protected], or KCSA Strategic Communications at [email protected].