On December 1, 2021 Alligator Bioscience AB (publ) ("Alligator" or the "Company") reported that the Company’s rights issue of shares (the "Rights Issue"), in which the subscription period ended on 26 November 2021, has been completed (Press release, Alligator Bioscience, DEC 1, 2021, View Source [SID1234596329]). The final count in the Rights Issue shows that 118,371,431 shares, corresponding to approximately 92.1 per cent of the Rights Issue, have been subscribed for by the exercise of subscription rights (including subscription undertakings). Furthermore, 37,602,276 shares were subscribed for without subscription rights, corresponding to approximately 29.3 per cent of the Rights Issue. The final outcome shows that the Rights Issue has been oversubscribed. Through the Rights Issue, Alligator receives approximately SEK 257 million before deduction of transaction costs.

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Outcome

The Rights Issue comprised a maximum of 128,499,507 ordinary shares, of which 118,371,431 shares, corresponding to approximately 92.1 per cent of the Rights issue, has been subscribed for by exercise of subscription rights. 37,602,276 shares, corresponding to approximately 29.3 per cent of the Rights Issue, has been subscribed for without the exercise of subscription rights. Thus, 155,973,707 shares, corresponding to approximately 121.4 per cent of the Rights Issue, has been subscribed for with and without the exercise of subscription rights. The Rights Issue is thus oversubscribed and no guarantee commitments have been utilized.

Notification regarding allocation

Allocation of shares has been made in accordance with the allocation principles described in the prospectus that was published in connection with the Rights Issue (the "Prospectus"). A notification regarding allocation of shares subscribed for without the exercise of subscription rights will be made by post of a settlement note to each subscriber. Allocated shares subscribed for without the exercise of subscription rights shall be paid for in accordance with the instructions in the settlement note.

Trading in BTA

Trading in BTA (Sw. betald tecknad aktie) is currently taking place at Nasdaq Stockholm and will cease when the Rights Issue has been registered by the Swedish Companies Registration Office, which is expected to take place around week 50, 2021. BTA:s will then be converted to ordinary shares.

Number of shares and share capital

The Rights Issue provides Alligator with proceeds amounting to approximately SEK 257 million before transaction costs. As a result of the Rights Issue, Alligator’s share capital will increase by SEK 51,399,802.80 to a total of SEK 85,666,338 and the total number of shares will increase by 128,499,507 shares to a total of 214,165,845 shares, all ordinary shares.

Guarantee Commitments

In connection with the Rights Issue, the Company has entered into agreements on guarantee commitments. For the guarantee commitments, a commission is paid, either in cash or in the form of newly issued shares in the Company. The subscription price for any shares issued to guarantors has been set to SEK 2.10, corresponding to 90 per cent of the volume-weighted average share price (VWAP) for the Company’s share on Nasdaq Stockholm during the subscription period in the Rights Issue (i.e. during the period 12 – 26 November 2021. In case all guarantors would choose to receive guarantee commission in shares, a total of a maximum of 10,660,763 new shares would be issued as guarantee commission.

Supplementary prospectus

With reference to a formatting error through which information about an individual guarantor (Nyenburgh Holding BV), as well as subtotals for subscription undertakings was mistakenly excluded from the Prospectus’ summary of guarantee commitments and subscription undertakings, the Company will prepare and publish a supplementary prospectus. The supplementary prospectus will be made available on the Company’s website.

Advisers

DNB Markets, a part of DNB Bank ASA, Sweden Branch and Redeye AB act as Joint Global Coordinators in connection with the Rights Issue. Setterwalls Advokatbyrå AB acts as legal adviser to Alligator and Baker & McKenzie Advokatbyrå KB acts as legal adviser to the Joint Global Coordinators in connection with the Rights Issue. Aktieinvest FK AB acts as the issuing agent in the Rights Issue.

On December 1, 2021 The National University Cancer Institute, Singapore ("NCIS") and MiNA Therapeutics Limited ("MiNA" or the "Company"), the pioneer in small activating RNA therapeutics, reported that the first patient has been dosed in an investigator-sponsored Phase 1 study of MiNA’s small activating RNA oligonucleotide, MTL-CEBPA, in combination with first-line standard of care, atezolizumab and bevacizumab, in patients with previously untreated, advanced hepatocellular carcinoma (HCC) (Press release, MiNA Therapeutics, DEC 1, 2021, View Source [SID1234596349]). Atezolizumab and bevacizumab are being provided by F. Hoffmann-La Roche, Ltd ("Roche") who is also supporting the study.

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The study has been designed by Principal Investigator Dr. Cheng Ean Chee, Senior Consultant at the Department of Haematology-Oncology, NCIS and supported by the Singapore Ministry of Health’s National Medical Research Council under its Centre Grant programme (CG; NMRC/CG/M005/2017_NCIS). The study will be conducted at NCIS’s clinical trial facility with the Haematology-Oncology Research Group (HORG) at the National University Hospital, Singapore.

This is a single-center, Phase 1, open label dose-escalation and dose expansion study of MTL-CEBPA, co-administered with atezolizumab and bevacizumab, in approximately 30 patients with unresectable or advanced HCC who have not previously received systemic therapy. The primary endpoint for the dose escalation phase will be determination of any dose-limiting toxicity, and the primary endpoint of the dose expansion phase will be objective response rate (ORR). The study is expected to read out top-line data in 2023.

Dr Cheng Ean Chee, Senior Consultant at the Department of Haematology-Oncology, NCIS, commented:

"Despite the recent progress of immunotherapies, advanced liver cancer remains a significant unmet medical need. With only 30% of patients benefiting from objective responses to first-line standard of care, new treatment combinations are needed in order to improve patient outcomes. We are excited to evaluate investigational agent MTL-CEBPA in combination with the current standard of care and we are glad to collaborate with MiNA Therapeutics and Roche."

Nagy Habib, Head of R&D at MiNA Therapeutics, commented:

"We are delighted to collaborate with the National University Cancer Institute, Singapore, and Roche to evaluate this new immunotherapy combination. In preclinical and clinical studies, MTL-CEBPA has been reported to improve the anti-tumour activity of leading oncology drugs by counteracting a new cancer immune evasion pathway which causes resistance to those drugs. Based on this data, we believe that MTL-CEBPA combinations have the potential to improve the standard of care significantly in patients with advanced HCC."

Dr Sivabalan Sivanesan, Medical Director at Roche Singapore, commented:

"Roche is both proud and excited to join this investigation of a new treatment combination in advanced HCC. Having established a role in metastatic HCC and other cancers, atezolizumab is currently being investigated in many different cancers including early HCC. With more than 70% of the global liver cancers being diagnosed in Asia, this is an amazing opportunity to study the role of a new combination with atezolizumab in HCC."

About MTL-CEBPA

MTL-CEBPA is the first therapy that specifically up-regulates CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and in solid tumour cancers have been identified as a critical barrier for many therapies to induce clinical responses. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppressive effect in the tumour micro-environment. MTL-CEBPA is currently in clinical development as a combination therapy for the treatment of advanced liver cancer and advanced solid tumour malignancies.

About atezolizumab and bevacizumab

Atezolizumab is a human monoclonal antibody IgG1 classified as a PD-L1 inhibitor, and functions by binding to PD-L1 and blocking the PD-1/PD-L1 interaction, thus restoring T-cell activation and antitumour responses.4 Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF). 4 The immunomodulatory effect of bevacizumab is expected to increase CD8-positive T-cell recruitment and relieve intratumoral immunosuppression, thereby boosting the effects of atezolizumab.

The results of the phase 3 study of atezolizumab plus bevacizumab vs sorafenib in untreated, advanced HCC patients has been published and an overall survival (OS) benefit was observed with the combination compared to sorafenib.4 The median OS in the atezolizumab plus bevacizumab group compared to those in sorafenib group was 19.2 mo vs 13.4 mo (HR 0.66, 95% CI: 0.52-0.85; P=0.0009).7 The trial also reported an updated objective response rate (ORR) of 29.8% with atezolizumab plus bevacizumab vs 11.3 % in sorafenib (per RECIST 1.1).7 The combination provides the longest survival seen in a front-line phase 3 study in advanced HCC, confirming atezolizumab plus bevacizumab as a standard of care for first line therapy in untreated, advanced HCC.

About hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the seventh most common cancer diagnosed and second most common cause of cancer deaths worldwide.1 It has an annual incidence of at least 840 000 patients1,2 with rising incidence in the developed world. HCC is an aggressive tumour that often occurs in the setting of chronic liver disease and cirrhosis and is often diagnosed late in its course, as there are no biomarkers to detect it when it is incipient and potentially curable. Treatment options are divided into surgical therapies and nonsurgical therapies. Curative therapies such as resection, transplantation, or percutaneous therapies benefit only 25% of patients. The majority of patients are not eligible for such therapies because of the extent of their tumour or underlying liver dysfunction. Improving treatment outcomes in patients with advanced stage hepatocellular carcinoma (HCC) requires the development of agents with tolerable safety profiles and the identification of biomarkers capable of predicting tumour response or resistance to treatment. The underlying aetiology for HCC development is often chronic viral infection and inflammation. Recently, the combination of atezolizumab (anti-PDL1) and bevacizumab (anti-VEGF) was approved by the FDA in 2020 for frontline therapy in advanced HCC based on an overall survival benefit compared to sorafenib.4 This has established atezolizumab and bevacizumab as a standard of care for first line therapy in untreated, unresectable or metastatic HCC. Sorafenib, a multikinase inhibitor, was approved by the FDA and globally in 2007 for treatment of advanced-stage HCC. In the past 4 years, additional systemic therapies have been approved for treatment of advanced HCC including other tyrosine kinase inhibitors such as lenvatinib, regorafenib, and cabozantinib; antibodies against VEGFR2 eg. ramucirumab; and anti-PD1 immunotherapy such as nivolumab. Overall response and survival benefit of all of these agents have been modest and highlight a need for better treatment in this disease.

On December 1, 2021 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported Janssen Biotech, Inc. (Janssen) received U.S. Food and Drug Administration (FDA) approval of DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in combination with Kyprolis (carfilzomib) and dexamethasone (Kd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy (Press release, Halozyme, DEC 1, 2021, View Source [SID1234596366]). This approval follows Janssen’s regulatory submission to the FDA in February 2021.

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"We are pleased that Janssen received U.S. FDA approval for the ninth indication for DARZALEX FASPRO in multiple myeloma, this time in combination with Kyprolis (carfilzomib) and dexamethasone," said Helen Torley, president and chief executive officer at Halozyme. "With its three-to-five-minute subcutaneous administration, DARZALEX FASPRO is now a treatment option for a broader range of patients suffering from multiple myeloma."

The FDA approval for DARZALEX FASPRO is based on data from Janssen’s PLEIADES Study, which met its primary endpoint of overall response rate. For more information about the PLEIADES study and its findings, please view Janssen’s press release issued today.

DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

On December 1, 2021 GlyTherix reported the award of a $50,000 COVID-19 TechVoucher by the NSW Government through Investment NSW that will provide funding support to collaborate with ANSTO’s world-leading radiochemistry and preclinical imaging teams (Press release, Glytherix, DEC 1, 2021, View Source [SID1234596313]). Funds will be used to generate new preclinical models to evaluate the efficacy, biodistribution, and pharmacokinetics of our lead cancer immunotherapy antibody, Miltuximab.

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Recent installation of start-of-the-art PET-CT and SPECT-CT imaging systems at ANSTO will facilitate high-resolution small animal imaging of Miltuximab.

The theranostic products produced and tested in this project will generate significant input for the design of our Phase Ib trial to ensure that safety and efficacy endpoints will be met with confidence.

Dr Brad Walsh, CEO GlyTherix, commented "We are extremely grateful to the NSW Government for their continued support of our important therapeutic program, particularly as we have a first-in-world radio-immunotherapy developed in NSW. Additionally, we are pleased that this strengthens our long collaboration with ANSTO who have partnered with us in developing this radioimmunotherapy. A win-win for NSW companies."

On December 1, 2021 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development and a strong emerging pipeline, reported that the U.S. Food and Drug Administration, or FDA, has granted orphan-drug designation for INBRX-109 for the treatment of chondrosarcoma (Press release, Inhibrx, DEC 1, 2021, View Source [SID1234596331]).

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"We believe orphan-drug designation underscores the recognition of INBRX-109 as a promising therapeutic for patients with metastatic or unresectable chondrosarcoma, a patient community currently with no other viable options," said Inhibrx Chief Executive Officer Mark Lappe.

The FDA’s Office of Orphan Products Development grants orphan designation status to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases, or conditions that affect fewer than 200,000 people in the U.S. Orphan-drug designation provides certain benefits, including financial incentives to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval.

About Chondrosarcoma

Chondrosarcoma is an orphan bone cancer with approximately 2,800 new patients diagnosed annually in the United States and the European Union. There are currently no therapeutics approved for the treatment of chondrosarcoma.

About INBRX-109

INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation.
In January 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma.
In November 2021, Inhibrx provided updated results from its ongoing Phase 1 clinical trial evaluating the efficacy and safety of INBRX-109 in patients with conventional chondrosarcoma. Preliminary disease control was observed in 16 of the 18 evaluable patients (89%) measured by RECISTv1.1, with two of the 18 achieving partial responses (11%). Based on preliminary results of the ongoing Phase 1 trial, the median progression-free survival (PFS) is 7.4 months, and the median overall survival has not been reached. Three patients have exceeded 61 weeks on treatment with INBRX-109, with 77 weeks being the longest duration of stable disease observed to date.

In June 2021, Inhibrx initiated a randomized, blinded, placebo-controlled, potential registration-enabling Phase 2 trial of INBRX-109 in conventional chondrosarcoma.