On June 17, 2024 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion" or the "Company"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported publication of data from its Phase 1 dose escalation study of its lead personalized cancer vaccine candidate, EVX-01, for metastatic melanoma (Press release, Evaxion Biotech, JUN 17, 2024, View Source [SID1234644383]). The study results, published in the Journal for ImmunoTherapy of Cancer, demonstrated that eight out of 12 patients (67%) experienced objective clinical responses (ORR) with six partial and two complete responses. Further, EVX-01 immunization did not induce vaccine-related serious adverse events in patients co-administered with anti-PD1 therapy.

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The EVX-01 cancer vaccine is designed to target neoantigens – antigenic sequences derived from cancer mutations – that are displayed on the surface of cancer cells, allowing the immune system to recognize, attack and eliminate the malignant cells. Since the neoantigen tumor profiles vary from one cancer patient to another, the EVX-01 cancer vaccine is truly personalized and tailored to the unique characteristics of each patient’s tumor and immune system profile. This represents a novel treatment paradigm with potential broad application in cancer therapy.

At this year’s ASCO (Free ASCO Whitepaper) annual meeting, the Company presented comprehensive immune data from its ongoing EVX-01 Phase 2 study, with 71% of the administered neoantigens inducing a specific T-cell response. Furthermore, a positive correlation between the neoantigen prediction score assigned by AI-Immunology and the reported induced immune response confirmed the Phase 1 study findings and further substantiated the predictive power of Evaxion’s AI platform.

"This publication provides a clear conclusion to our Phase 1 study, with peer-reviewed validation of our reported outcomes. We are very impressed with EVX-01 achieving a 67% objective response rate in the trial. This is encouraging as it verifies a true reduction in tumor burden following dosing and compares favorably with historical data from anti-PD-1 monotherapy trials. With the encouraging data from our ongoing Phase 2 study of EVX-01 presented at this year’s annual ASCO (Free ASCO Whitepaper) meeting, we are on track to report our one-year readout in the third quarter of this year," said Christian Kanstrup, CEO of Evaxion.

For more information about the recent EVX-01 Phase 2 immune data presented at ASCO (Free ASCO Whitepaper), please visit our recent press release.

About EVX-01 Phase 2 Clinical Trial

EVX-01 is Evaxion’s lead clinical asset and constitutes a peptide-based personalized cancer vaccine. The ongoing Phase 2 clinical study is a self-sponsored, open-label, single-arm, multi-center trial carried out in collaboration with Merck Sharp & Dohme LLC, together with leading principal investigators and research centers from Italy and Australia. It aims to evaluate the efficacy and safety of EVX-01 vaccination in combination with the anti-PD1 treatment pembrolizumab (more commonly known as KEYTRUDA) in treatment-naive patients with metastatic or unresectable malignant stage III or IV melanoma. More information can be accessed under clinical trial ID NCT05309421.

On June 17, 2024 Charles River Laboratories International, Inc. (NYSE: CRL) and Captain T Cell, a spinoff from the renowned Max Delbrück Center Berlin, Germany, reported a plasmid DNA and retrovirus vector production program agreement (Press release, Captain T Cell, JUN 17, 2024, View Source [SID1234644408]). As part of Charles River’s Cell and Gene Therapy (CGT) Accelerator Program (CAP), Captain T Cell will have access to established plasmid and viral vector contract development and manufacturing organization (CDMO) capabilities and advisory services ahead of Captain T Cell’s plan to manufacture a TCR-T cell therapy for solid tumor patients for a Phase I clinical trial.

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An Award-winning Approach to Cancer Immunotherapy
With the goal to give new patient groups access to T cell immunotherapies, Captain T Cell is developing efficacy-enhanced treatment options for solid tumor therapies. Using a toolbox of next-generation technologies, Captain T Cell generates T cells displaying tumor-specific T cell receptors (TCR) as well as enhanced persistence and the capacity to cope with the hostile tumor microenvironment of difficult-to-treat solid tumors. Once infused into a patient’s body, these tumor-specific T cells intend to find and destroy tumor cells. This therapeutic method may provide an option for patients with tumors that no longer respond to other therapies.

Cell and Gene Therapy CDMO Solutions
To bring its gene-modified cell therapy to clinic, Captain T Cell will leverage Charles River’s established plasmid and viral vector production capabilities, finetuned over decades supporting CGT developers from pre-clinical to commercial scale.

In recent years, Charles River has significantly broadened its cell and gene therapy portfolio with several acquisition integrations and expansions to simplify complex supply chains and meet growing demand for plasmid DNA, viral vector, and cell therapy services. Combined with its legacy testing capabilities, Charles River offers a premier "concept-to-cure" advanced therapies solution.

Approved Quotes
"We are thrilled to work with the Captain T Cell team to support the manufacture of its TCR-T cell cancer immunotherapy. Charles River has decades of success reliably manufacturing plasmid DNA, viral vectors, and cell therapies, helping to safeguard our customer programs and bring potential therapies to patients with limited options." – Kerstin Dolph, Corporate Senior Vice President, Global Manufacturing, Charles River

"Captain T Cell is devoted to developing a new generation of toolbox-engineered T cell-based immunotherapies for solid tumor patients. We have the utmost confidence in the expertise of Charles River as we work to bring our lead candidate to the clinic." – Felix Lorenz, CEO, Captain T Cell

On June 17, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported the launch of a capital increase through issuance of new shares for a minimum of €2.2 million gross proceeds (Press release, TME Pharma, JUN 17, 2024, View Source [SID1234644409]). Guaranteed net proceeds will allow the company to reach key strategic partnering and financing milestones in 2024.

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The operation is open to professional investors and is also open to the retail investors in France via the PrimaryBid platform for up to €390,000, representing up to 15% of the total capital increase. A separate guarantee agreement has been put in place to ensure the company will have received €2.2 million gross by June 28, 2024. Guaranteed net proceeds will extend cash runway from July 20241 into December 2024, past targeted strategic partnering and financing milestones in Q4-2024.

"NOX-A12 has delivered exceptional data in chemotherapy-resistant patients with the aggressive brain cancer, glioblastoma, in combination with radiotherapy and the anti-VEGF antibody bevacizumab: a 10-fold increase in the rate of survival at 21 months when compared to a reference cohort receiving standard of care (50% vs 5%) and a near-doubling of the median overall survival (19.9 vs. 10.5 months)2. This strong clinical data enabled TME Pharma to fulfill its promises to: 1) obtain FDA approval for the Phase 2 trial design in brain cancer, 2) obtain Fast Track designation and access to the accelerated regulatory pathway from the FDA, 3) raise funds to eliminate convertible debt from the capital structure of the company, and 4) generate a high-profile scientific publication around NOX-A12 such as Nature Communications article announced earlier today," said Aram Mangasarian, CEO of TME Pharma. The guaranteed capital injection announced today will provide TME Pharma with financing into December 2024, with the possibility of extending our cash runway even further should the outstanding Warrants Z be exercised between July 1 and the end of 2024. This increased financial visibility will allow us to focus on achievement of our next targeted strategic partnering and financing milestones for 2024, which include: cooperation with a pharma partner on drug supply of the anti-VEGF antibody combination drug for the Phase 2, monetization of the NOX-E36 asset (e.g. via a spinout) and additional transactions sufficient to secure financing of the upcoming Phase 2 NOX-A12 brain cancer trial via a combination of non-dilutive grant funding, a strategic alliance and/or investment from expert institutional investors. In summary, our goal for this financing is to allow a significant transformation of the company’s profile in the remainder of 2024."

Key Financing details and timetable

Capital increases as part of a transaction comprise:
a public offering in France only through the French PrimaryBid platform for up to €390,000, or up to 15% of the total capital increase for retail investors (and not in any other jurisdiction including without being exclusive the Netherlands or any other EU/EEA Member State, the United Kingdom, the United States of America, Australia, Canada or Japan) under the exemption and subject to the applicable publication requirement listed in the French Code monétaire et financier and the General Regulation of the Autorité des marchés financiers (AMF) and falling within one or more of the exemptions from any requirement for the company to publish a prospectus pursuant to the prospectus regulation within the meaning of Regulation (EU)2017/1129 of the European Parliament and of the Council of June 14, 2017, as amended (the PrimaryBid Offering); and
a reserved offering to professional investors within the European Union by way of private placement with an accelerated book-build (the Reserved Offering) with the minimum of €2.2 million excluding the PrimaryBid Offering.
The price of €0.1798 per new share, representing a discount of 10% to the closing price on June 17, 2024.
The PrimaryBid Offering will close on June 17, 2024, at 10.00 p.m. Paris time and the Reserved Offering will close on June 18, 2024, before start of trading (subject to early closure).
A group of guarantors are contractually committed guarantee €2.2 million in gross proceeds by June 28, 2024, by purchasing new shares at the same price of €0.1798 per share, in exchange for a 10% fee on the guaranteed amount. This ensures that even if today’s capital increase does not reach its targeted amount, net proceeds from the guarantors will extend cash runway into December 2024, past targeted strategic partnering and financing milestones in Q4-2024.
The company will announce the results of the transaction as soon as possible following the closing of the order book for the Reserved Offering in a press release, which will present the final number of new ordinary shares issued.
Settlement of the new shares and their admission to trading on Euronext Growth Paris multilateral trading facility are expected to occur on June 20, 2024. The new shares will be of the same class and fungible with the existing shares, will carry all rights attached to the shares, and will be admitted to trading under the same ISIN code NL0015000YE1.
Use of Proceeds

Approximately 30% of net proceeds from the capital increase will be used on research and development (R&D) activities including ongoing NOX-A12 GLORIA Phase 1/2 trial in brain cancer, regulatory interactions in Europe for the next brain cancer trial and intellectual property activities. Another approximately 30% of net proceeds will be used for outreach to potential industry partners and investors, the pursuit of government or charitable grants and preparation for the targeted monetization of the NOX-E36 program. The remaining 40% of net proceeds will be used for general corporate purposes including accounting, auditing, legal advice and maintenance of the listing.

Guarantee

Gross proceeds of €2.2 million is guaranteed by a group of investors, whose individual commitment is not representing a concerted action towards the potential control of the company. None of them individually would cross threshold of 50% ownership even if the guarantee was required in full.

Shareholder and Corporate Authorizations

The issuance of shares in this transaction relies upon the authorizations granted to the Issuer by its shareholders in the annual general meeting (AGM) on June 29, 2023, under agenda items 5 and 6. Issuer has completed and obtained all necessary corporate approvals for the transaction. In particular, at the AGM held on June 29, 2023, the company’s shareholders approved the transitional provision which came into effect in February 2024, as a result the authorized capital amounts to €900,000 divided into 80,000,000 ordinary shares and 10,000,000 preference shares, each share with a nominal value of €0.01.

Dilutive Potential

Shareholders residing in France have the option to participate via the PrimaryBid platform to reduce dilution from this transaction if they are able to purchase sufficient number of shares. If they do not participate in the PrimaryBid Offering they will be diluted as outlined in the table below.

Table: Dilutive Potential from Transaction

Description

Shares to be issued
(max)

Total shares
outstanding

Dilution (max)

Shareholder
starting with 1%
would then hold

Prior to announcement of capital increase

–

28,453,373

–

1%

Up to €2,590,000 capital increase at €0.1798 per share

14,404,894

42,858,267

33.61%

0.66%

Financial Intermediaries

ALLinvest is the global coordinator – lead manager and bookrunner for the Reserved Offering.
For the PrimaryBid Offering, retail investors will be able to subscribe exclusively through the PrimaryBid partners indicated on the PrimaryBid website (www.PrimaryBid.fr). The PrimaryBid Offering is not covered by an underwriting agreement. For further details, please refer to the PrimaryBid website at www.PrimaryBid.fr.

Risk Factors

The main risk factors relating to the transaction are as follows:

the market price of the company’s shares may fluctuate and fall below the subscription price of the new shares, resulting in a loss for investors;
the volatility and liquidity of the company’s shares may fluctuate significantly;
existing shareholders will see their stake in the company’s share capital diluted;
the placement is not subject to a performance guarantee and investors who have acquired shares could sustain a loss equal to the price of acquiring these shares if the company is not able to continue its operations due to strategic, operational or financial factors;
the company expects to incur losses for the foreseeable future and will need substantial additional funding from industrial partners, financial investors, and/or governmental or charitable institutions in order to complete the development and commercialization of its product candidates, which may not be available on acceptable terms when needed, if at all.
Before deciding to invest, investors are asked to familiarise themselves with the risks described in the company’s 2023 annual financial report available on the company website.

Potential Conflict of Interest

Part of the variable remuneration of management relates to corporate goals for advancing the development pipeline of TME Pharma as well as securing the respective funding. Management also holds shares, warrants and options in the company.

On June 17, 2024, Illumina, Inc. ("Illumina" or the "Company") reported to have entered into a 364-day delayed draw credit agreement (the "Credit Agreement") among the Company, as the borrower, the lenders from time to time party thereto and JPMorgan Chase Bank, N.A., as administrative agent (in such capacity, the "Administrative Agent") (Filing, 8-K, Illumina, JUN 17, 2024, View Source [SID1234644385]).

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The Credit Agreement provides for a senior unsecured term loan credit facility in an aggregate principal amount of up to $750 million (the "Credit Facility") which can be drawn on a delayed draw basis at any time prior to the earliest of (i) the termination of the definitive agreement in respect of the GRAIL Transactions (as defined below), (ii) the consummation of the GRAIL Transactions without the funding of the Credit Facility, (iii) May 5, 2025, if the GRAIL Transactions have not occurred prior to such date, and (iv) the date on which the Company notifies the Administrative Agent that it is terminating the commitments under the Credit Facility, for a 364-day term. Any loans under the Credit Facility will have a variable interest rate based on either the term secured overnight financing rate or the alternate base rate, plus an applicable rate that varies with the Company’s debt rating and, in the case of loans bearing interest based on the term secured overnight financing rate, a credit spread adjustment equal to 0.10% per annum. The current borrowing rate under the Credit Facility is approximately 6.70%.

The proceeds of the loans under the Credit Facility may be used to fund cash to the balance sheet of GRAIL, LLC ("GRAIL"), in connection with the Company’s planned divestment of GRAIL (the "GRAIL Transactions").

The Credit Agreement contains financial and operating covenants. The financial covenant provides for a maximum total leverage ratio. Operating covenants include, among other things, limitations on (i) the incurrence of indebtedness by the Company’s subsidiaries, (ii) liens on assets of the Company and its subsidiaries and (iii) certain fundamental changes and the disposition of assets by the Company and its subsidiaries. The Credit Agreement contains other customary covenants, representations and warranties, and events of default.

Amounts borrowed under the Credit Facility may be prepaid, and the commitments under the Credit Facility may be terminated by the Company, at any time without premium or penalty (other than customary breakage costs). As of the date of this report, no borrowings were outstanding under the Credit Facility. The Credit Facility is expected to be drawn in full on June 20, 2024, and therefore the Credit Facility is expected to mature, and all amounts outstanding thereunder would become due and payable in full, on June 19, 2025.

The foregoing summary of the Credit Agreement is qualified in its entirety by the full text of the Credit Agreement, which is attached as Exhibit 10.1 hereto and is incorporated herein by reference.

On June 17, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported the publication of biomarker data from the GLORIA Phase 1/2 clinical trial of NOX-A12 in brain cancer (glioblastoma) in the peer-reviewed scientific journal Nature Communications (Press release, TME Pharma, JUN 17, 2024, View Source [SID1234644410]).

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The article by Dr. Frank A. Giordano at the University Medical Center Mannheim and members of the five other centers in Germany led by a translational research team at the University of Bonn, entitled "L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial", details a potential predictive biomarker known as the "EG12 score" for glioblastoma patients treated with NOX-A12 and radiotherapy.

The EG12 score is calculated by analyzing the frequency of positivity for NOX-A12’s target, CXCL12, on two key cell types in the glioblastoma tumor microenvironment: endothelial (E) and glioma (G) cells. The score significantly correlated with the clinical outcome, in terms of progression-free survival (PFS) for patients treated with NOX-A12 and radiotherapy (r = 0.87; p = 0.005), but not for a cohort of reference patients with comparable characteristics treated with standard of care (r = 0.13; p = 0.56). As such, the biomarker appears to be specific for response to NOX-A12-based therapies. When dividing the trial population into two groups in the middle by its EG12 score, GLORIA patients with higher EG12 scores had a significantly longer median PFS than those with lower scores (6.0 vs. 3.0 months; p = 0.031) and also a strong trend towards improved median overall survival (15.8 vs. 11.1 months; p = 0.075).

The research on the EG12 predictive biomarker published in Nature Communications builds on data first presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2023.

"The publication of this scientific article in the prestigious peer-reviewed journal Nature Communications is a validation of the groundbreaking biomarker data from our GLORIA trial in aggressive adult brain cancer and builds on the earlier presentation of these findings at one of the world’s top cancer conferences," said Aram Mangasarian, CEO of TME Pharma. "A predictive biomarker has many potential advantages, not the least the ability to select patients who will most benefit from our NOX-A12-based therapies. This could help us identify target populations for future clinical trials, enhancing their statistical power and de-risking the further overall clinical development of NOX-A12. It also offers investors and potential partners peer-reviewed evidence of the potential of our glioblastoma program to bring benefit to patients suffering from this complex and underserved indication as we advance NOX-A12 toward Phase 2 evaluation."

The full article is available online on Nature Communications’ website.