On September 28, 2022 Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) (the "Company"), a specialty vaccine company, reported its intention to issue and sell, subject to market conditions, approximately $40 million of its ordinary shares in a global offering to specified categories of investors comprised of (i) a public offering of its American Depositary Shares ("ADSs"), each representing two ordinary shares, in the United States (the "U.S. Offering") and (ii) a concurrent private placement of its ordinary shares in certain jurisdictions outside of the United States (the "European Private Placement" and together with the U.S. Offering, the "Global Offering") (Press release, Valneva, SEP 28, 2022, View Source [SID1234621556]).

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Goldman Sachs, Jefferies, Guggenheim Securities and Bryan, Garnier & Co. are acting as joint bookrunners for the Global Offering.

All securities to be sold in the Global Offering will be offered by the Company. The ADSs are listed on the Nasdaq Global Select Market under the symbol "VALN," and the Company’s ordinary shares are listed on the regulated market of Euronext in Paris ("Euronext") under the symbol "VLA."

The offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros, as well as the number of ADSs and ordinary shares sold in the Global Offering, will be determined following a book building process commencing immediately. The price per ordinary share (and corresponding offering price per ADS) will be at least equal to the weighted average price of the Company’s ordinary shares on Euronext over a period, chosen by the Company’s Management Board, of between three (3) and ninety (90) consecutive trading days preceding the determination of the offering price, reduced by a maximum discount of 15%, if applicable.

The ADSs and/or ordinary shares will be issued through a capital increase without shareholders’ preferential subscription rights and for the benefit of a specified category of persons within the meaning of Article L.225-138 of the French Commercial Code (Code de commerce) and pursuant to the 24th resolution of the Company’s annual combined general meeting held on June 23, 2022. Under the authority granted by the shareholders in the 24th resolution, the ordinary shares and ADSs may only be purchased initially by (i) natural persons and legal entities, including companies, trusts or investment funds, organized under French or foreign law, that routinely invest in the pharmaceutical, biotechnological or medical technology sector; and/or (ii) companies, institutions or entities of any type, French or foreign, that do a significant part of their business in the pharmaceutical, cosmetic, chemical or medical devices and/or technologies or research in these sectors. In order to purchase ordinary shares and/or ADSs in the Global Offering, potential investors will be required to execute and provide to the Underwriters an investor letter representing that they satisfy the foregoing investor criteria.

The European Private Placement will be open only to qualified investors as such term is defined in article 2(e) of Regulation (EU) 2017/1129 of the European Parliament and of the Council of June 14, 2017.

The closing of the U.S. Offering and the European Private Placement will occur simultaneously, will be conditioned on each other and are expected to occur on the third trading day after the final pricing and allocation of the Global Offering. The underwriting agreement to be entered into among the Company and the underwriters for the Global Offering (the "Underwriters") will not constitute a performance guarantee (garantie de bonne fin) within the meaning of Article L.225-145 of the French Commercial Code.

The Global Offering will commence immediately and the Company plans to announce the result of the Global Offering as soon as practicable after pricing thereof in a subsequent press release. The Company expects to use the net proceeds from the Global Offering to finance the co-development and marketing of its vaccine candidate against Lyme disease (VLA15), to finance the development and marketing of its vaccine candidate against the chikungunya virus (VLA1553), to finance the development of two of its preclinical vaccine candidates, VLA1554 and VLA2112, and the remainder, if any, for working capital and for general corporate purposes.

Bpifrance Participations S.A., which is an existing shareholder, has indicated an interest in purchasing up to an aggregate of €5.0 million of the ordinary shares in the Global Offering at the offering price. However, because indications of interest are not binding agreements or commitments to purchase, the Underwriters may determine to sell fewer or no ordinary shares in the Global Offering to Bpifrance Participations S.A., or Bpifrance Participations S.A. may determine to purchase fewer or no ordinary shares in the Global Offering. The representative of Bpifrance Participations S.A. to the Company’s Supervisory Board (Conseil de Surveillance) did not take part in the vote on the decisions (relating to the approval for the launch of the global offering and for the delegation of authority) at the meeting of the Supervisory Board of Directors (Conseil de Surveillance) held on September 24, 2022.

A shelf registration statement on Form F-3 relating to the ADSs and ordinary shares in the Global Offering was filed with the U.S. Securities and Exchange Commission ("SEC") on August 12, 2022 and was declared effective on August 19, 2022. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities in any jurisdiction, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction. The securities sold will not be part of a public offering in France. The registration statement, including the prospectus and a preliminary prospectus supplement, can be accessed by the public on the website of the SEC.

The securities referred to in this press release will be offered in the United States only by means of a prospectus approved by the SEC. When available, copies of the preliminary prospectus relating to and describing the terms of the Global Offering may be obtained from: Goldman Sachs & Co. LLC, Attn: Prospectus Department, 200 West Street, New York, New York 10282, telephone: 866-471-2526, facsimile: 212-902-9316, e-mail: [email protected] or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at +1 877 821 7388 or by email at [email protected].

Application will be made to list the new ordinary shares to be issued pursuant to the Global Offering on the regulated market of Euronext in Paris pursuant to a listing prospectus (the "Listing Prospectus") subject to the approval by the Autorité des Marchés Financiers ("AMF") and comprising (i) the 2021 universal registration document filed with the AMF on March 23, 2022 (document d’enregistrement universel 2021) under number D. 22-0140 (the "2021 URD"), as completed by an amendment to the 2021 URD expected to be filed with the AMF on September 30, 2022 (the "Amendment") and (ii) a securities note (Note d’opération) (the "Securities Note"), including (iii) a summary of the prospectus. Copies of the Company’s 2021 URD, as amended, will be available free of charge on the Company’s website. The Listing Prospectus will be published on the Company’s website and on the AMF’s website (www.amf-france.org).

On September 28, 2022 Xuanzhu Biopharm, a novel drug subsidiary of Sihuan Pharm based in Jinan, reported that it has filed for an IPO on the Shanghai STAR Exchange that would raise $345 million (Press release, Xuanzhu Biopharmaceutical, SEP 28, 2022, View Source [SID1234621540]). Now 20 years old, Xuanzhu has developed a portfolio of more than 25 small molecule and biologic candidates, including two NDA stage products. The company has built a 400-member team led by returnee scientists that develops new drugs through its own R&D without depending on in-licensings or CROs. Earlier this year, Xuanzhu completed a $96 million Series B financing.

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On September 28, 2022 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported the commercial availability of Karl Storz’s New Blue Light equipment powered by Saphira in the U.S. As part of the rollout, Karl Storz plans to host a Virtual Launch event for the medical community streamed from its El Segundo, California office where Sia Daneshmand M.D. and Kristin Scarpato M.D. M.P.H. will discuss the clinical benefits of using BLC with Cysview for NBMIC*, while sharing their perspectives on the advantages that the New Blue Light system provides over the original system for TURBT**. The Virtual Launch event is scheduled to take place on October 13, 2022 at 4:00pm Pacific Time.

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"We are pleased to share that Karl Storz has begun filling Obsolescence Protection Program (OPP) orders for customers who purchased New Blue Light system upgrades last year," said Geoff Coy, Vice President and General Manager, North America. "Orders for the new Saphira system appear to be outpacing orders from the past signaling pent up demand for the advanced technology, and we expect to begin filling new account orders in the fourth quarter. Given the strong demand, we continue to believe that BLC is on its way to becoming the standard of care for endoscopic visualization of bladder cancer."

"Uro-oncologists and their staff have expressed a strong desire to have the new Blue Light system at their hospitals, and the upcoming Virtual Launch Event is an opportunity to showcase the system’s benefits and broaden awareness of BLC in the market," said Ken Pugh, Head of North America Marketing and Alliance Management. "Accordingly, we are working diligently with our partners to ensure that all customers who want The New Blue Light, have it for all appropriate patients with NMIBC."

Dr. Sia Daneshmand, M.D., is Professor of Urology with Clinical Scholar designation and serves as director of clinical research as well as the urologic oncology (SUO) fellowship director at the University of Southern California (USC) in Los Angeles.

Dr. Kristin Scarpato, M.D., M.P.H., is Associate Professor Department of Urology residency program director and vice chair of education for the Department of Urology, Division of Urologic Oncology at Vanderbilt University Medical Center in Tennessee.

*NMIBC: Non-muscle invasive bladder cancer

**TURBT: Transurethral resection of bladder tumor

Note to editors:

Hexvix/Cysview and BLC are registered trademarks of Photocure ASA. IMAGE1 S and Saphira are registered trademarks of KARL STORZ Endoscopy.

This press release may contain product details and information which are not valid, or a product that is not accessible, in your country. Please be aware that Photocure does not take any responsibility for accessing such information, which may not comply with any legal process, regulation, registration, or usage in the country of your origin.

About Bladder Cancer

Bladder cancer ranks as the 8th most common cancer worldwide – the 5th most common in men – with 1 720 000 prevalent cases (5-year prevalence rate)1a, 573 000 new cases and more than 200 000 deaths in 2020.1b

Approx. 75% of all bladder cancer cases occur in men.1 It has a high recurrence rate with up to 61% in year one and up to 78% over five years.2 Bladder cancer has the highest lifetime treatment costs per patient of all cancers.3

Bladder cancer is a costly, potentially progressive disease for which patients have to undergo multiple cystoscopies due to the high risk of recurrence. There is an urgent need to improve both the diagnosis and the management of bladder cancer for the benefit of patients and healthcare systems alike.

Bladder cancer is classified into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of invasion in the bladder wall. NMIBC remains in the inner layer of cells lining the bladder. These cancers are the most common (75%) of all BC cases and include the subtypes Ta, carcinoma in situ (CIS) and T1 lesions. In MIBC the cancer has grown into deeper layers of the bladder wall. These cancers, including subtypes T2, T3 and T4, are more likely to spread and are harder to treat.4

1 Globocan. a) 5-year prevalence / b) incidence/mortality by population. Available at: View Source, accessed [January 2022]
2 Babjuk M, et al. Eur Urol. 2019; 76(5): 639-657
3 Sievert KD et al. World J Urol 2009;27:295–300
4 Bladder Cancer. American Cancer Society. View Source

About Hexvix/Cysview (hexaminolevulinate HCl)

Hexvix/Cysview is a drug that preferentially accumulates in cancer cells in the bladder, making them glow bright pink during Blue Light Cystoscopy (BLC). BLC with Hexvix/Cysview, compared to standard white light cystoscopy alone, improves the detection of tumors and leads to more complete resection, fewer residual tumors, and better management decisions.

Cysview is the tradename in the U.S. and Canada, Hexvix is the tradename in all other markets. Photocure is commercializing Cysview/Hexvix directly in the U.S. and Europe and has strategic partnerships for the commercialization of Hexvix/Cysview in China, Chile, Australia, New Zealand and Israel. Please refer to View Source for further information on our commercial partners.

On September 28, 2022 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") ( Nasdaq: CTXR), a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products, reported that the Company has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for denileukin diftitox (I/ONTAK), an engineered IL-2-diphtheria toxin fusion protein for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) (Press release, Citius Pharmaceuticals, SEP 28, 2022, View Source [SID1234621534]). I/ONTAK is a purified and more bioactive formulation of previously FDA-approved ONTAK. The BLA is supported by a pivotal Phase 3 study (NCT01871727). Results of the study were consistent with the prior FDA-approved formulation.

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"The treatment of advanced cutaneous T-cell lymphoma remains a complex and challenging unmet medical need. Each year, thousands of patients are diagnosed with CTCL, a debilitating orphan disease with no single standard of care. Patients are often treated with multiple alternate therapies. Citius is proud to advance the only potential CTCL therapeutic with a mechanism of action that delivers a cytotoxic protein by binding to the IL-2 receptors found in malignant T-cells and immunosuppressive T-regulatory cells. We look forward to continuing to engage with the FDA as they review our BLA and bringing this treatment option to patients, if approved," stated Leonard Mazur, Chairman and CEO of Citius. "The BLA filing for denileukin diftitox marks the first of our pipeline candidates to be submitted for FDA approval."

About I/ONTAK
I/ONTAK is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. I/ONTAK, a purified version of denileukin diftitox, is a reformulation of previously FDA-approved oncology treatment ONTAK. ONTAK was marketed in the U.S. from 1999 to 2014, when it was voluntarily withdrawn from the market. Manufacturing improvements resulted in a new formulation, which maintains the same amino acid sequence but features improved purity and bioactivity. The new formulation received regulatory approval in Japan in 2021 for the treatment of CTCL and peripheral T-cell lymphoma (PTCL). In 2011 and 2013, the FDA granted orphan drug designation (ODD) to I/ONTAK for the treatment of PTCL and CTCL, respectively.

About Cutaneous T-cell Lymphoma
Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple systemic agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL. Approximately 3,000 new cases are reported in the United States every year, with an estimated 30,000 – 40,000 individuals living with the disease.

On September 28, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that ASTRUM-005, an international multi-centre study led by Professor Ying Cheng, has been published in The Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world (Press release, Shanghai Henlius Biotech, SEP 28, 2022, View Source [SID1234621533]). ASTRUM-005 trial is a phase 3 study of HANSIZHUANG (serplulimab), an anti-PD-1 monoclonal antibody (mAb) developed by Henlius independently, plus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). After Prof. Ying Cheng orally presented them at the 2022 ASCO (Free ASCO Whitepaper) annual meeting, the results of ASTRUM-005 attract wide attention among the global research community. And now, ASTRUM-005 makes its way to the international arena once again, demonstrating the high level of academic acclaim on a global scale, the intelligence of Chinese researchers, and the strength of Chinese pharmaceuticals in terms of independent innovation research and clinical development.

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Prof. Ying Cheng, the corresponding author and first author, as well as the leading principal investigator of the study, from Jilin Cancer Hospital, said, "In the ASTRUM-005 trial, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC. Compared with chemotherapy, the treatment prolonged median OS by 4.5 months and had the lowest HR of 0.63. In addition, the study showed good safety and consistent efficacy over time. ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC. It is also the first international multi-centre phase 3 clinical study led by Chinese researchers to employ immunotherapy for ES-SCLC treatment, showcasing the expertise and excellence of Chinese researchers. I would like to thank all patients and their families, as well as researchers who contributed to this study. It opens a new chapter in first-line ES-SCLC immunotherapy, which will benefit a large number of patients."

OS 15.4 months, a new record

SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases. Both limited stage SCLC (LS-SCLC) and ES-SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC. At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines at home and abroad as the first-line treatment for ES-SCLC. Compared with chemotherapy, the overall survival (OS) of patients with SCLC has been prolonged to a certain extent, but the improvements were still modest, suggesting the need for more effective treatments in this patient population.

ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy in previously untreated patients with ES-SCLC. ASTRUM-005 has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.5% were White. As of data cutoff for this interim analysis (October 22, 2021), 585 eligible patients were randomised (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. Median OS was significantly longer in the serplulimab group (15.4 months, 95% confidence interval [CI] 13.3-not evaluable) than in the placebo group (10.9 months, 95% CI 10.0-14.3) (hazard ratio [HR] 0.63, 95% CI 0.49-0.82; P <0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median progression-free survival assessed by an independent radiology review committee per RECIST v1.1 was also longer in the serplulimab group compared to the placebo group (5.7 months vs. 4.3 months; HR 0.48, 95% CI 0.38-0.59). Incidence of immune-related adverse events (irAEs) was similar to the approved PD-1/PD-L1 antibodies.

Providing more treatment options for patients worldwide

The success of ASTRUM-005 is a breakthrough in the treatment of ES-SCLC with PD-1 inhibitors. Based on the results of ASTRUM-005, the New Drug Application (NDA) of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA). Furthermore, HANSIZHUANG has been recommended for the first-line treatment of ES-SCLC by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC.

In April 2022, the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of SCLC. Based on the positive feedback from FDA Biologics License Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion on the FDA’s Type C consultation meeting, Henlius is planning to soon carry out a bridging study in the US and expected to submit BLA to FDA before Q1 of 2024. At present, there is no anti-PD-1 mAb approved for the first-line treatment of SCLC worldwide. HANSIZHUANG is expected to become the world’s first anti-PD-1 mAb for the first-line treatment of SCLC and to fill the clinical gap in the next five years.