On March 23, 2023 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the European Medicines Agency (EMA) has validated the application for its self-developed anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab), in combination with chemotherapy (carboplatin and etoposide), for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Shanghai Henlius Biotech, MAR 23, 2023, View Source [SID1234629266]). The European Commission (EC) previously granted Orphan Drug Designation (ODD) to HANSIZHUANG for the treatment of small cell lung cancer (SCLC).

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"HANSIZHUANG is Henlius’ first innovative mAb, as well as the first and only anti-PD-1 therapy approved for treatment of SCLC, which has benefited 13,000 SCLC patients in China. Since launched in March 2022, it has been approved for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer and ES-SCLC in China," said Jason Zhu, President of Henlius. "HANSIZHUANG is steadily making its way from China to Europe and the U.S. Previously, we had Zercepac approved in more than 30 countries including the European Union. We hope HANSIZHUANG will further open that market and spur global expansion as we seek to benefit more patients."

Enhance the global presence

The regulatory application is based on data from ASTRUM-005, a randomized, double-blind, placebo-controlled international multi-centre phase 3 clinical study, which evaluated the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with ES-SCLC. The study has set up a total of 128 sites in various countries including China, Poland, Turkey, and Georgia, and enrolled 585 subjects, among whom 31.5% were White. The results of ASTRUM-005 were presented in oral for the first time at the 2022 ASCO (Free ASCO Whitepaper) annual meeting and was then 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, which made ASTRUM-005 the first study published on JAMA in SCLC immunotherapy, demonstrating the high level of academic acclaim on a global scale.

In 2022, HANSIZHUANG was also granted ODD by the Food and Drug Administration (FDA) for the treatment of SCLC. The ODD granted by the FDA is beneficial for the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States (U.S.). Based on the positive feedback of FDA Biologics license Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion results of the FDA’s Class C consultation meeting, Henlius has initiated a bridging head-to-head trial in U.S. patients with ES-SCLC to evaluate the efficacy of HANSIZHUANG, which propels the product towards U.S. market approval further.

More are on the horizon

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius and has since seen benefits in 19,000 patients in China. Its synergy with in-house products of the company and innovative therapies are being actively promoted and 14 clinical trials on immuno-oncology combination therapies are in progress in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. In addition to the launched indications of sqNSCLC and ES-SCLC, Henlius also explored to treat patients with non-squamous non-small cell lung cancer (nsNSCLC) and limited-stage small cell lung cancer (LS-SCLC). Recently, the first patient has been dosed in an international multi-centre phase 3 clinical trial of HANSIZHUANG (serplulimab) in patients with LS-SCLC in the U.S. In the field of gastrointestinal cancer, HANSIZHUANG has been approved for the treatment of MSI-H solid tumours, which could benefit patients with MSI-H colorectal cancer and MSI-H gastric cancer. It was also recommended for the first-line treatment of esophageal cancer (category IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer and its NDA for the first-line treatment of esophageal squamous cell carcinoma (ESCC) was accepted by the NMPA based on the data of ASTRUM-007, which was published in Nature Medicine (IF: 87.241). In addition, PD-1 inhibitors are less explored in neoadjuvant/adjuvant therapies for gastric cancer, and Henlius has led the way with a phase 3 clinical study, striving to benefit gastric cancer patients from the early line of immunotherapy.

Through overseas development of HANSIZHUANG, Henlius will accelerate the pace of global internationalisation and deliver more high-quality, affordable treatment options to patients.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 3 indications are approved for marketing in China, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC). The marketing applications of the first-line treatment for esophageal squamous cell carcinoma (ESCC) and ES-SCLC are under review by the NMPA and the EMA, respectively. Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 14 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,500 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA, IF: 157.3), Nature Medicine (IF: 87.241), and the British Journal of Cancer (IF: 9.075), respectively. Furthermore, HANSIZHUANG was respectively recommended for the first-line treatment of ES-SCLC in the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) and the treatment of esophageal cancer (category IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer. Serplulimab was also granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC.

On March 23, 2023 Bayer reported that it has further expanded the global clinical development program for the oral androgen receptor inhibitor (ARi) darolutamide in prostate cancer (Press release, Bayer, MAR 23, 2023, View Source [SID1234629265]). The new Phase III clinical study, ARASTEP, will investigate the efficacy of darolutamide plus androgen deprivation therapy (ADT) versus ADT alone in hormone-sensitive prostate cancer, in patients with high-risk biochemical recurrence (BCR) who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. BCR is defined as rising prostate-specific antigen (PSA) levels with a doubling time of <12 months after primary treatment (surgery or radiotherapy).1,2 Darolutamide is already approved under the brand name NubeqaTM for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease as well as metastatic hormone-sensitive prostate cancer (mHSPC). Bayer estimates that the peak sales potential for Nubeqa will exceed €3 billion.

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"Many patients with rising PSA levels following surgery or radiation are at an increased risk of developing metastasis. With ARASTEP, we are optimistic about the potential to help patients at this earlier stage of the disease," said Tara Frenkl, M.D., Senior Vice President and Head of Oncology Development at Bayer. "Darolutamide has already demonstrated efficacy and safety in nmCRPC with the Phase III ARAMIS trial, and in mHSPC with the Phase III ARASENS trial. Our goal is to ensure that as many patients as possible benefit from this therapy, therefore we continue to assess the potential of darolutamide in earlier disease stages."

The study is part of a robust global clinical development program for darolutamide. The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence.

Darolutamide is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

About the ARASTEP Trial
The ARASTEP trial is a randomized, double-blind, placebo-controlled Phase III study of darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in hormone-sensitive prostate cancer, in patients with high-risk biochemical recurrence (BCR) who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. The primary endpoint of this study is radiological progression-free survival (rPFS), measured by PSMA PET/CT assessed by independent central review. The trial is expected to enroll approximately 750 participants. Patients will be randomized to receive the standard regimen of 600 mg of darolutamide twice a day or matching placebo plus ADT.

About hormone-sensitive prostate cancer and biochemical recurrence (BCR)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.3

Hormone-sensitive prostate cancer is a type of prostate cancer that needs androgens (male hormones) to grow and therefore stops growing when androgens are not present. Almost all early-stage prostate cancers are androgen-dependent.4

Up to 50% of patients with prostate cancer develop elevated prostate-specific antigen (PSA) levels in their blood after primary therapy (surgery and/or radiation therapy).5 This disease state is called biochemical recurrence (BCR). Current treatment options for patients with biochemical recurrent prostate cancer include prostatectomy, intending to be curative. If these treatments are unsuccessful, androgen deprivation therapy (ADT) is an option to control disease.2

About darolutamide (NubeqaTM)
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. This is supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial6 and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.7

The product is approved under the brand name Nubeqa in more than 80 countries around the world for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S., Japan, China and the EU. Filings in other regions are underway or planned.

About Prostate Cancer at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. Prostate cancer is the second most commonly diagnosed cancer in men3 and a key area of focus for Bayer. The company’s franchise includes two products on the market (Nubeqa and Xofigo) and several compounds in development, including a unique approach of advancing targeted alpha therapies. Bayer is focused on addressing the unique needs of prostate cancer patients, providing treatments that extend their lives throughout the different stages of the disease and allowing them to continue their everyday activities, so that they can live longer, better lives.

On March 23, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, and Pangea Biomed, a company combining machine learning and deep RNA analysis to expand access to precision oncology, reported a research collaboration between the companies (Press release, Onconova Therapeutics, MAR 23, 2023, View Source [SID1234629264]). The collaboration will leverage Pangea Biomed’s proprietary algorithmic platform, ENLIGHT, with the goal of identifying biomarkers of response to Onconova’s proprietary investigational product candidate rigosertib.

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Rigosertib has a multi-faceted mechanism of action targeting proteins containing the RAS binding domain, allowing it to modulate the PI3K and PLK1 pathways, as well as the tumor immune microenvironment. Clinical data have suggested the anti-cancer activity of rigosertib plus checkpoint inhibition in KRAS-mutated non-small cell lung cancer, and of rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa, an ultra-rare condition driven by PLK1 overexpression.

"Rigosertib’s ability to potently inhibit PLK1 and modulate the tumor immune microenvironment confers broad potential to treat a range of solid cancers," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "By leveraging Pangea’s AI platform to identify predictive biomarkers of response to rigosertib, we aim to inform a precision medicine approach to selecting additional PLK1-dependent tumors and other indications for its potential evaluation. We believe this approach will increase the probability of success for rigosertib’s future development programs."

"Precision medicine is the future of oncology, but gaps in the industry’s current biomarker approaches overly narrow patient populations for promising drugs," said Pangea Biomed Chief Executive Officer Tuvik Beker, Ph.D. "ENLIGHT goes beyond standard biomarkers to expand patient populations for targeted therapies, in addition to surfacing new biomarkers for existing drugs. We’re hopeful our platform can help Onconova accelerate rigosertib’s successful development in a variety of difficult-to-treat cancers."

Pangea Biomed’s ENLIGHT platform is a pan-cancer response predictor that evaluates in vitro, preclinical, and clinical datasets to build genetic interaction maps that infer functional relationships between gene pairs to reveal tumor vulnerabilities to specified therapies. Onconova and Pangea Biomed will chart genetic interactions related to PLK1 to identify a biomarker of response to rigosertib based on its inhibitory activity against this protein. The ENLIGHT platform will then be applied to generate additional genetic interaction maps around other pathways targeted by rigosertib. Per a collaboration agreement between the companies, Onconova retains all rights to rigosertib and will own intellectual property that may result from the research collaboration.

On March 23, 2023 Moderna, Inc. (Nasdaq:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and Generation Bio Co. (Nasdaq:GBIO), a biotechnology company innovating genetic medicines for people living with rare and prevalent diseases, reported that the two companies have entered into a strategic collaboration to combine Moderna’s biological and technical expertise with core technologies of Generation Bio’s non-viral genetic medicine platform (Press release, Moderna Therapeutics, MAR 23, 2023, View Source [SID1234629263]). The collaboration aims to expand the application of each company’s platform by developing novel nucleic acid therapeutics, including those capable of reaching immune cells, to accelerate their respective pipelines of non-viral genetic medicines.

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"Moderna continues to invest in innovative technology to enable us to develop a breadth of transformative medicines for patients," said Rose Loughlin, Ph.D., Moderna’s Senior Vice President for Research and Early Development. "Through this collaboration, which builds on Generation Bio’s non-viral genetic medicines platform, we have the potential to target immune cells with diverse nucleic acid cargos and the liver for gene replacement. We are excited to have Generation Bio as our partner as we continue to broaden our therapeutic pipeline and extend the potential benefit of nucleic acid therapeutics to more patients."

"Non-viral DNA therapeutics may offer durable, redosable, titratable genetic medicines to patients suffering from rare and prevalent diseases on a global scale," said Phillip Samayoa, Ph.D., Chief Strategy Officer of Generation Bio. "This collaboration represents a foundational investment in our platform science, both deepening our pipeline of rare and prevalent liver disease programs beyond hemophilia A and accelerating our work to reach outside of the liver with nucleic acid therapies. We are thrilled to collaborate with Moderna to extend genetic medicines to new tissues and cell types through the joint development of novel targeting for our stealth ctLNPs to reach immune cells."

About the Collaboration

Under the terms of the agreement, Moderna may advance two immune cell programs, each of which may use a jointly developed ctLNP to deliver ceDNA. In addition, Moderna may advance two liver programs, each of which may use a liver-targeted ctLNP developed by Generation Bio to deliver ceDNA. Moderna retains an option to license a third program for either immune cells or the liver.

Generation Bio will receive a $40 million upfront cash payment and a $36 million equity investment issued at a premium over recent share prices. Moderna will fund all collaboration work, including a research pre-payment. Generation Bio is also eligible for future development, regulatory and commercial milestone payments, as well as royalties on global net sales of liver-targeted and immune cell-targeted products commercialized under the agreement. The agreement additionally provides Moderna with the right, subject to certain terms and conditions, to purchase additional shares of common stock in connection with a future equity financing by Generation Bio.

Further, Moderna and Generation Bio will both leverage collaboration research to continue to advance in vivo immune cell targeting as a new class of genetic medicines, with downstream economics on products utilizing such technology. Generation Bio is eligible to receive certain exclusivity fees as well as potential development and regulatory milestones and royalties on products that Moderna advances using ctLNP technology developed under the collaboration.

On March 23, 2023 Sirona Biochem Corp. (TSX-V: SBM) (FSE: ZSB) (OTC: SRBCF) ("Sirona" or the "Company") reported a non-brokered private placement offering of unsecured, convertible debentures (the "Convertible Debentures") (Press release, Sirona Biochem, MAR 23, 2023, View Source [SID1234629262]). The Company is offering Convertible Debentures units (the "Debenture Units") at a price of $1,000 per Debenture Unit for aggregate gross proceeds of up to $1,500,000 (the "Offering").

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Each Debenture Unit will have a face value of (the "Face Value") of $1,120, consisting of $1,000 in principal (the "Principal") and $120 in prepaid interest (the "Prepaid Interest"). The Principal of the Debenture Units will accrue interest at a rate of 12% per annum, which accrued interest ("Accrued Interest") will be paid semi-annually, in arrears. The Company will pay the Prepaid Interest and Accrued Interest in cash or, subject to TSX Venture Exchange ("TSXV") acceptance, may elect to satisfy payment in kind by issuing Shares ("Interest Shares"). In the event of payment in kind, the number of Interest Shares due will be calculated using a conversion price (the "Interest Conversion Price") equal to, subject to acceptance by the TSXV, the maximum Discounted Market Price (as defined in TSXV policies) on the applicable payment due date.

The holder may, at its option, convert in full or in part, the Principal at any time prior to the maturity date (the "Maturity Date"), being the third anniversary of the issue date, into units (the "Units") of the Company at $0.10 per Unit (the "Conversion Price"). Upon conversion of the Principal, the Company will pay Prepaid Interest and unpaid Accrued Interest in cash or, subject to acceptance by the TSXV, in Interest Shares issued at the Interest Conversion Price.

Each Unit will consist of one Share and one non-transferable share purchase warrant (a "Warrant"). Each Warrant will be exercisable by the holder thereof to purchase one Share (a "Warrant Share") at an exercise price of $0.15 at any time prior to the Maturity Date.

The Company shall have the right to redeem the Convertible Debentures prior to the Maturity Date at any time after 6 months from the issue date, by paying holders in cash the Face Value of the Convertible Debentures, together with all Prepaid and Accrued Interest and a redemption penalty payment of 8% of the Face Value. The Company shall give the holders 30 business days’ notice (the "Redemption Notice") to do so. On receipt of a Redemption Notice, a holder may elect to convert all or part of the Principal of the Convertible Debenture into Units at the Conversion Price. All Prepaid and Accrued Interest in respect of the Principal amount so converted shall be, at the election of the holder, either paid in cash or, subject to acceptance by the TSXV, converted into Shares at the Interest Conversion Price, by giving the Company notice (the "Conversion Notice") within 10 business days of receipt of the Redemption Notice.

The closing of the Offering is subject to the receipt of necessary regulatory approvals, including the approval of the TSXV. The Convertible Debentures, Shares, Warrants and any Warrant Shares will be subject to a four-month hold period under applicable securities laws and TSXV policies. The Company may pay eligible finders a fee in connection with the Offering.

The Company plans to use approximately 1/3 of the net proceeds from the Offering for general corporate purposes, and the remainder of the proceeds will used for research and development expenses (including but not limited to, laboratory staff salaries, laboratory materials and intellectual property costs).

Dr. Howard Verrico, the Chief Executive Officer, has agreed to subscribe for $500,000 of Debenture Units. Dr. Verrico’s participation is a "related party transaction" within the meaning of Multilateral Instrument 61-101 Protection of Minority Security Holders in Special Transactions. The Company intends to rely on the exemptions from the formal valuation and minority shareholder-approval requirements of MI 61-101 in respect of related party participation in the Offering. The MI 61-101 exemptions are available as the fair market value of the Debenture Units, and the fair market value of the consideration for the Debenture Units, insofar as it involves Dr. Verrico and other interested parties, will not exceed 25% of the Company’s market capitalization.

This news release does not constitute an offer to sell or the solicitation of any offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful. The Convertible Debentures and the Shares which may be issued on exercise thereof have not been and will not be registered under the United States Securities Act of 1933, as amended (the "U.S. Securities Act") and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the U.S. Securities Act and applicable state securities laws.