On January 7, 2021 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported that the GBM AGILE pivotal study (NCT03970447) has commenced recruitment to the paxalisib arm (Press release, Kazia Therapeutics, JAN 7, 2021, View Source [SID1234573609]).

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Key Points

GBM AGILE is an international adaptive, multi-drug study, designed to expedite the development of new therapies for glioblastoma

Kazia executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) in October 2020 to bring paxalisib into GBM AGILE

Lead investigators for the paxalisib arm are Professor Ingo Mellinghoff (Memorial Sloan Kettering Cancer Center) and Dr Eudocia Q Lee (Dana-Farber Cancer Institute)

Positive data from GBM AGILE is expected to support registration of paxalisib in the US and other key markets

Kazia CEO, Dr James Garner, commented, "we are delighted to have recruitment underway, and this marks an important milestone for Kazia as we begin the new year. The GBM AGILE study has secured the support of leading clinicians in the glioblastoma field, and has increasingly won the confidence of regulators and industry participants, so we are excited to be a part of it. If the data from GBM AGILE is positive, we expect it to provide a basis for registration in glioblastoma, and it therefore represents an important step towards commercialisation of the drug.

Clinical Trial Design

The paxalisib arm of GBM AGILE will recruit newly diagnosed patients with the unmethylated MGMT promotor, a genetic marker that denotes near-total resistance to temozolomide, the existing FDA-approved standard of care. In addition, the study will recruit recurrent patients who have progressed despite treatment with temozolomide. The adaptive design allows GBM AGILE to balance between these two patient groups according to emerging data, so it is possible for paxalisib to emerge successful in one or both populations. The primary endpoint of GBM AGILE is overall survival, which is considered the gold standard for the evaluation of new cancer therapies, and which is the preferred approval endpoint for regulators such as the US FDA.

The study will recruit up to 200 patients on paxalisib in total, and these will be compared against a roughly similar number of patients in a control group, with patients being randomly allocated between the groups. The total data set for paxalisib will therefore include up to approximately 450 patients from GBM AGILE. The duration of paxalisib’s enrolment is initially estimated to be approximately 30-36 months. However, the adaptive design of GBM AGILE means that if a definitive conclusion is evident at an earlier stage, the study will conclude at that point, with a commensurate reduction in timelines and cost.

Further information was provided in Kazia’s announcement to the ASX on 16 October 2020.

Operational Update on GBM AGILE

GBM AGILE commenced operation in July 2019. The first drug to join the study was regorafenib (Bayer), which is an approved therapy for other solid tumours. Kazia Therapeutics’ paxalisib and Kintara Therapeutics’ VAL-083 commenced recruitment in January 2021.

At present, GBM AGILE is operational in over 30 centres across the United States and has screened over 370 patients to date. The study is expected to open sites in Canada, Europe, and China during CY2021.

The first site to open to the paxalisib arm is the Henry Ford Cancer Institute in Detroit, MI, under the oversight of Dr Tom Mikkelsen. It is expected that other sites will rapidly open to the paxalisib arm as they receive approval from their Institutional Review Boards.

Paxalisib Clinical Program

GBM AGILE is one of eight ongoing clinical trials of paxalisib in brain cancer.

On January 7, 2021, Iovance Biotherapeutics, Inc. Presented its corporate presentation (Press release, Iovance Biotherapeutics, JAN 7, 2021, View Source [SID1234573608]).

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On January 7, 2021 Addex Therapeutics Ltd (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, reported the pricing of an underwritten global offering of 6,000,000 registered shares (the New Shares) (including shares in the form of American Depositary Shares, or ADSs) at a public offering price of approximately CHF1.47 per share or $10.00 per ADS (Press release, Addex Therapeutics, JAN 7, 2021, View Source [SID1234573607]). Each ADS represents the right to receive six shares of Addex. The aggregate gross proceeds from the offering are expected to be $10.0 million, before deducting the underwriting discounts and commissions and offering expenses payable by Addex. The offering is expected to close on or about January 11, 2021, subject to satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

In connection with the offering, Addex has granted the underwriter a 30-day option to purchase up to additional 900,000 shares (or ADSs) at the public offering price, less the underwriting discounts and commissions.

The New Shares will be issued from existing authorized share capital of Addex under exclusion of the existing shareholders’ pre-emptive rights.

The New Shares, if issued, are expected to be listed and admitted to trading on SIX Swiss Exchange. The New Shares will rank pari passu with Addex’s existing shares.

The shares, including those to be settled in the form of ADSs, are being offered and sold pursuant to the Company’s previously filed registration statement on Form F-1 (File No. 333-251322), as amended, with the U.S. Securities and Exchange Commission (SEC) and declared effective by the SEC on January 6, 2021. The offering is being made by means of a prospectus. When available, an electronic copy of the final prospectus relating to, and describing the terms of, the offering may be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (646) 975-6996 or e-mail at [email protected] or on the SEC’s website at SEC.gov.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. There is no intention or permission to publicly offer, solicit, sell or advertise, directly or indirectly, any securities of Addex Therapeutics Ltd in or into Switzerland within the meaning of the Swiss Financial Services Act ("FinSA"). Neither this document nor any other offering or marketing material relating to these securities, such as the shares, constitutes or will constitute a prospectus pursuant to the FinSA, and neither this document nor any other offering or marketing material relating to the shares constitutes a prospectus pursuant to the FinSA, and neither this document nor any other offering or marketing material relating to the shares may be publicly distributed or otherwise made publicly available in Switzerland.

On January 7, 2021 The Executive Board of Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY; the "Company") reported that with the consent of the Supervisory Board, to issue a subordinated mandatory convertible bond in an aggregate principal amount of up to EUR 5,500,000.00 (Press release, Epigenomics, JAN 7, 2021, View Source [SID1234573606]). It may be converted into up to a total of 5,000,000 registered no-par value shares of the Company with a share in the Company’s share capital of up to a total of EUR 5,000,000.00.

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The mandatory convertible bond consists of up to 500,000 notes with a nominal amount of EUR 11.00 each, which will be offered for subscription at an issue price of EUR 11.00 each by means of a rights offering initially to the existing shareholders of Epigenomics AG. Shareholders will be given the option of over-subscription. The rights offering is scheduled for publication on the Company’s website (www.epigenomics.com) and in the German Federal Gazette on January 11, 2021. The subscription period for the Company’s shareholders is scheduled to start on January 13, 2021 and to end on January 27, 2021 (including each of these two days). Epigenomics AG has signed a back-stop agreement with its shareholder Deutsche Balaton Aktiengesellschaft, under which Deutsche Balaton Aktiengesellschaft has undertaken to acquire notes in an aggregate principal amount of up to EUR 4,000,000.00 by exercising its subscription rights and by the acquisition of notes not subscribed for via subscription rights and oversubscription rights. An application has been made for the subscription rights to be traded on the open market of the Hamburg Stock Exchange.

The notes are non-interest-bearing (zero coupon) and have a term until February 29, 2024. In addition to the conversion rights of the holders or creditors of the bonds, the terms and conditions of the bonds also include a conversion obligation for all outstanding notes not yet converted on February 29, 2024.

Subject to any anti-dilution adjustments, the conversion price per share is EUR 1.10 and the conversion ratio is 1:10. This means that each note is convertible into ten no-par value shares with a share in the Company’s share capital of EUR 1.00 per share.

Epigenomics AG plans to use the proceeds from the issue of the mandatory convertible bond to finance its business operations. The proceeds primarily serve to mitigate the financial pressure to act following the pending announcement of the final decision by the U.S. Centers for Medicare & Medicaid Services (CMS) in connection with the ongoing reimbursement process for the Epi proColon colorectal cancer screening test in the U.S.A. (National Coverage Determination, NCD) and not to be dependent on the capital market environment in the short term. Furthermore, the funds will help to financially secure any delay in the announcement of the CMS decision.

M.M. Warburg & CO (AG & Co.) Kommanditgesellschaft auf Aktien is acting as sole underwriter of the transaction.

On January 7, 2021 Werewolf Therapeutics, Inc., an oncology biotherapeutics company advancing a pipeline of next-generation, transformative cancer treatments, reported the completion of its $72 million Series B financing (Press release, Werewolf Therapeutics, JAN 7, 2021, View Source [SID1234573603]). The proceeds from the Series B financing will advance Werewolf’s lead INDUKINE product candidates, WTX-124 (interleukin-2, or IL-2) and WTX-330 (interleukin-12, or IL-12) through Phase 1 clinical proof-of-concept studies, and progress additional programs to Investigational New Drug application-readiness. INDUKINE molecules are a novel class of systemically delivered, conditionally activated proinflammatory immune modulators.

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The financing was led by RA Capital Management and joined by new investors Deerfield Management, HBM Healthcare Investments, Soleus Capital, Adage Capital, Sphera Healthcare and CaaS Capital. Also participating in the financing were Werewolf’s Series A investors including MPM Capital, Longwood Fund, Taiho Ventures, Arkin Bio Ventures, UPMC Enterprises and DC Investment Partners. In connection with the closing of the financing, Derek DiRocco, Ph.D. of RA Capital Management and Elise Wang of Deerfield Management joined the Board of Directors of Werewolf.

"This commitment from a world-class syndicate of life science investors propels Werewolf’s pipeline of potentially transformative immunomodulatory biotherapeutics into clinical development while leveraging our powerful PREDATOR protein engineering platform to identify and optimize new product candidates," said Daniel J. Hicklin, Ph.D., Founder and Chief Executive Officer of Werewolf Therapeutics. "We intend to use the proceeds from this financing to accelerate our preclinical research and discovery, advance our two lead programs to the clinic, and attract the talent needed to realize our vision of translating powerful proinflammatory mechanisms into cancer therapies that deliver a clinically meaningful impact for patients."

In support of these initiatives, Werewolf will continue adding to its team of proven oncology drug developers, building upon the recently announced appointments of Randi Isaacs, M.D. as Chief Medical Officer, and Ellen Lubman as Chief Business Officer.

"While existing cytokine therapies are known to be effective treatments for patients with cancer, resulting in cures in some instances, efficacy is not maximized due to poor tolerability. The Werewolf platform of next-generation conditionally activated cytokines aims to optimize the safety of these immunotherapies so their full efficacy can be realized and allow for combination approaches to be tested" said Derek DiRocco, Ph. D., Partner at RA Capital Management. "RA Capital is excited to support the accomplished team at Werewolf as they advance their portfolio of INDUKINE immuno-therapies into the clinic with the goal of improving outcomes for patients with cancer."

"Werewolf is positioned to become a clear leader in one of the most exciting areas of cancer treatment research and development," added Elise Wang, Partner on the Structured Finance group at Deerfield Management Company. "While immunotherapy ranks among the greatest recent advances for people living with cancer, using the body’s immune system without eliciting off-target side effects remains a challenge. We are thrilled to support Werewolf as it advances its molecules into the clinic."

Werewolf is developing treatments, administered as monotherapy or in combination with other therapies such as checkpoint inhibitors, designed to enhance the body’s immune response to cancer. These treatments leverage well-validated and emerging proinflammatory immunomodulators, including cytokines such as IL-2, IL-12 and IFNα, that have been challenging to develop as systemically delivered therapeutics due to toxicities associated with exposure to normal, non-tumor tissue. The company uses its proprietary PREDATOR protein engineering platform to create conditionally activated proinflammatory INDUKINE molecules that can be systemically administered in an inactive form. Upon entering the tumor microenvironment, the INDUKINE molecules are selectively activated to deliver the full biological potency of cytokines and to recruit a powerful anti-tumor immune response for maximum therapeutic potential, while minimizing unwanted off-target effects in non-tumor tissue.

In preclinical studies, Werewolf’s lead product candidates exhibited anti-tumor activity and favorable pharmacokinetic and safety profiles. The company was founded through an initial investment by MPM Capital, which also co-led with Longwood Fund the Company’s $56 million Series A financing.