On December 7, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a pharmaceutical company focused on the development of targeted therapies for difficult-to-treat hematological diseases reported that the company will host a webcast on Wednesday, December 9th, 2020, at 14:00 (CET) to provide an update regarding the data presented December 4-8 at the American Society Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2020 (Press release, Oncopeptides, DEC 7, 2020, View Source [SID1234572282]).

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At ASH (Free ASH Whitepaper) Oncopeptides has presented twelve abstracts, including one oral presentation. Key clinical abstracts focused on new data from the ongoing phase 1/2 ANCHOR combination study and new data from the pivotal phase 2 HORIZON study. The preclinical abstracts further explored the mechanism of action of the proprietary peptide-drug conjugate platform in multidrug resistant models of multiple myeloma.

The webcast will be hosted by CEO Marty J Duvall, CSO Jakob Lindberg and CMO Klaas Bakker.

About melflufen
Melflufen (INN melphalan flufenamide) is a first in class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately hydrolyzed by peptidases to release an entrapped hydrophilic alkylator payload. Aminopeptidases are overexpressed in tumor cells and are even more pronounced in advanced cancers and tumors with a high mutational burden. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies. In the pivotal phase 2 HORIZON study melflufen plus dexamethasone demonstrated encouraging efficacy and a clinically manageable safety profile in heavily pretreated patients with relapsed refractory multiple myeloma, with primarily hematologic Adverse Events (AE) and a low incidence of non-hematologic AEs.

On December 7, 2020 GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and chronic liver diseases, reported that it has signed bond repurchase agreements with holders of its convertible bonds maturing in October 2022 (the "OCEANEs") (Press release, Genfit, DEC 7, 2020, https://ir.genfit.com/news-releases/news-release-details/genfit-announces-successful-completion-key-milestone-partial [SID1234572281]).

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Pascal Prigent, CEO of GENFIT, commented: "We are delighted to have reached this key milestone, and would like to thank the OCEANE holders who supported the Company’s buyback proposal for the significant efforts they have made to support the company’s future evolution. The restructuring of the OCEANEs is an important step in the execution of our corporate strategy and I am confident that our shareholders and OCEANE holders will now vote in favor of this transaction. Indeed, it will enable us to operationally and financially implement our strategic plan focused on the development of elafibranor in ELATIVE, our Phase 3 PBC trial, as well as further expand our NIS4 technology for NASH diagnosis. The current deal structure essentially cuts our debt in half and pushes its maturity to Q4 2025, which should give us ample opportunity to maximize the commercial potential of our assets and create significant value for bond holders and shareholders alike."

Final results of the partial buyback, and amendments of the existing terms and conditions of the OCEANEs

Following competition of the fixed-price reverse bookbuilding process begun on November 23, the Company has signed bond repurchase agreements with OCEANEs holders to buyback a total of 2,895,260 OCEANEs at a price of €16.40 per OCEANE, representing a total repurchase price of 47.48 million euros.

The repurchased OCEANEs represent 47.6% out of the 6,081,081 outstanding OCEANEs and 85,699,696 euros in nominal amount.

Following the cancellation of the OCEANEs that will be repurchased in the partial buyback, 3,185,821 OCEANEs would remain outstanding, representing a residual nominal amount of 94,300,301.6 euros.

The settlement of the OCEANEs buyback remains contingent on – and will occur after – the approval by GENFIT shareholders and OCEANEs holders of the following adjustments to the terms:

New maturity date of October 16, 2025;
Increase of the conversion ratio from 1:1 to 1:5.5, resulting in an implied conversion price of €5.38 per share;
Deferral of the initiation of the early redemption period1 in the OCEANEs terms and conditions (initiating on November 3, 2023); and
Amendment of the ratchet clause, adjusting the conversion ratio in the event of a tender offer targeting GENFIT shares, to incorporate the extension of the OCEANEs maturity date until 2025. The adjustment would be calculated from the date of approval by the OCEANEs holders of the amended terms and conditions (i.e. the date on which the OCEANEs holders meeting would be held) until the new maturity date (i.e. October 16, 2025).

(The "OCEANEs Amendments")

The nominal value and redemption price of the OCEANEs will remain unchanged at €29.60 per OCEANE. The existing terms and conditions of the OCEANEs not mentioned above will remain unchanged.

In order to obtain approval of the OCEANEs Amendments, the Company will convene a general meeting of its shareholders on January 13, 2021. Should the quorum not be achieved, a second shareholders meeting will be convened on January 25, 2021, in addition to an OCEANEs bondholder general meeting on January 25, 2021.

The buyback price of €16.40 includes the accrued interest for the period since the latest interest payment date, on October 16, 2020, until the buyback settlement date, expected to be January 29 2021, at the latest. For illustrative purposes, should an effective buyback date occur on January 29, 2021, the buyback price per bond (excluding accrued interests) would be €16.10, and the accrued interest amount would be €0.30. A change in the buyback settlement date (either earlier or later) will not lead to any change of the buyback price2.

Should the new conversion ratio be accepted, the implied conversion price (nominal amount of €29.60 divided by the 1:5.5 conversion ratio) would be €5.38 per bond. This represents a conversion premium3 of 18.8% compared to the closing share price on December 4, 2020 (€4.53), and a 32.2% premium compared to the volume weighted average price between November 16 and November 20, 2020 (i.e. the five trading days prior to the announcement of the final terms of the transaction on November 23, 2020)4.

Based on the new conversion ratio, 17,522,016 new shares could be issued upon conversion5 of all OCEANEs remaining post-buy-back, representing 45.1% of the current share capital of the Company (versus 15.6% with the current conversion ratio). In the event of a full conversion of the OCEANEs at maturity, the OCEANEs holders would own 31.08% of the share capital of the Company, and 30.8% should all the outstanding stock options and share warrants (BSA) be exercised, and all the outstanding free shares vest (based on instruments outstanding as of December 31, 2019).

Independent Expert and Prospectus

Following recommendation of a committee composed of a majority of independent directors, the Company’s Board of Directors has appointed an independent expert to review the balance of the terms of the transaction between the shareholders and OCEANE holders. This has been done on a voluntary basis and the report will be made publicly available.

As a result of the new conversion ratio, in the event of a full conversion of the OCEANEs outstanding post-buyback, the number of shares that would potentially be issued, would be higher than 20% of the share capital6 and the Company will file with the French Autorité des Marchés Financiers (AMF) a listing prospectus composed of the Company’s 2019 Universal Registration Document filed with the AMF on May 27, 2020 under number D.20-0503, an amendment of this Universal Registration Document, a securities note (note d’opération) and a summary of the prospectus, for approval by the end of December 2020.

Additional information relating to the convening of the shareholders’ extraordinary general meeting

Due to the ongoing lockdown and prohibition on public gatherings currently imposed by the French government to prevent the spread of Covid-19, the Board of Directors of the Company decided that the extraordinary shareholders’ meeting will be held behind closed doors, that is to say without the presence of shareholders and other persons who are usually entitled to attend, in accordance with the provisions of article 4 of Ordinance no. 2020-321 of March 25, 2020 adapting the rules for meeting and deliberation of meetings and governing bodies of legal persons and entities without legal personality of private law due to the Covid-19 epidemic, which application period has been extended and terms have been modified by the Ordinance no. 2020-1497 of December 2, 2020.

The convening notice published in the French legal announcements bulletin (Bulletin des Annonces Légales Obligatoires) and made available in the Investors & Media section of the Company’s website (https://ir.genfit.com/financial-information/shareholders-meeting) outlines the procedures by which shareholders may participate in the shareholders’ extraordinary general meeting, notwithstanding the exceptional measures required in order to comply with regulatory constraints and ensure the health and safety of our shareholders.

Shareholders may provide their voting instructions via the Internet through the VOTACCESS platform. A tutorial to familiarize shareholders with this online voting platform will be available in the same section of the website, as well as a toll-free number (France only: 0800 94 06 51) to call with any questions regarding how to participate to the shareholders’ extraordinary general meeting.

In accordance with Article 3 of Ordinance no. 2020-1497 of December 2, 2020, the Company will broadcast the shareholders’ extraordinary general meeting live except if technical reasons make it impossible or severely trouble such broadcast. The Company will also ensure a replay of such broadcast. Every written question asked by shareholders, together with the answers given in accordance with the third and fourth paragraphs of Article L. 225-108 of the French Code de commerce, will be published in the dedicated section of the Company’s website provided for in the fourth paragraph of such article.

Documentation regarding the shareholders’ extraordinary general meeting will be made available to shareholders in accordance with existing regulations on the Company’s website, in the Investors & Media section (https://ir.genfit.com/financial-information/shareholders-meeting).

Further details on the convening of the OCEANEs holders’ meeting to be held on January 25, 2020 will be made available later on.

Anticipated Calendar of Events

December 7, 2020 Publication of the convening notice (avis de reunion valant convocation) of the shareholders’ extraordinary general meeting
December 16, 2020 Publication of the meeting notice (avis de réunion) of the OCEANEs holders’ general meeting
Before end of December 2020 Submission of the amendment to the Universal Registration Document and approval of the prospectus by the AMF
Publication of the prospectus
January 13, 2021 Shareholders’ extraordinary general meeting upon first convocation
Press release announcing the results of the shareholders’ extraordinary general meeting or, due to the required quorum not being reached, second convening notice (avis de convocation) of the shareholders extraordinary general meeting
January 25, 2021 Shareholders’ extraordinary general meeting upon second convocation
OCEANEs holders’ general meeting
January 27, 2021 Decision of Chief Executive Officer authorising the OCEANEs Amendments
January 29, 2021
(at the latest) OCEANEs partial buyback settlement date

On December 7, 2020 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that results from the NOPHO sponsored Phase 2 trial of eryaspase in ALL patients, which were presented by Dr. Line Stensig Lynggaard at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting yesterday (Press release, ERYtech Pharma, DEC 7, 2020, View Source [SID1234572280]). In a webcast later today, Dr. Birgitte Klug Albertsen, Associate Professor at Aarhus University Hospital, Denmark, and Principal Investigator of the trial, will comment on the data and be available for Q&A.

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The Phase 2 NOR-GRASPALL-2016 trial evaluated the safety and pharmacological profile of eryaspase in ALL patients who had previously experienced hypersensitivity reactions to pegylated asparaginase therapy. The trial was conducted by the Nordic Society of Pediatric Hematology and Oncology (NOPHO) at 21 clinical sites in the Nordic and Baltic countries of Europe and enrolled 55 patients. Primary objectives of the trial were asparaginase enzyme activity and safety. Both endpoints were met.

Eryaspase demonstrated sustained asparaginase enzyme activity above the threshold of >100 U/L at trough levels, 14 days after first infusion in 54 of the 55 patients treated.

Eryaspase was generally well tolerated when added to chemotherapy and almost all patients were able to receive the intended courses of asparaginase (median of 5 doses per patient). Of the 55 patients, only 2 patients had severe allergic reaction and withdrew eryaspase treatment.

Dr Line Stensig Lynggaard, the study leader for NOPHO, commented: "Maintaining adequate asparaginase treatment following hypersensitivity to PEG-asparaginase remains an important goal when treating patients with ALL. A global shortage of supply Erwinia-derived asparaginase, which is the current alternative treatment option to PEG-asparaginase, highlights the need for new alternative treatment options. Our study has demonstrated that eryaspase, given as a convenient schedule every two weeks, provides a sustained asparaginase enzyme activity level, few hypersentivity reactions and is generally well tolerated in combination with chemotherapy. We conclude that eryaspase is an attractive treatment alternative for ALL patients with hypersensitivity to PEG-asparaginase."

"We are proud to be working with the NOPHO group in conducting this study in ALL and very grateful to them for presenting the findings at ASH (Free ASH Whitepaper) this year. The full study results provide the possibility of an alternative treatment for ALL patients with hypersensitivity to PEG-asparaginase" said Dr. Iman El-Hariry, ERYTECH’s Chief Medical Officer. "We look forward to discussing further the potential path forward for eryaspase in ALL with regulatory authorities, including the FDA".

A related eryaspase poster will be presented by Dr. Frank Hoke (ERYTECH’s Head of Clinical Pharmacology) on Monday 7th December 2020 from 8am PST / 11am EST / 5pm CET.

Abstract #2799: Population Pharmacokinetics of Eryaspase in Patients with Acute Lymphoblastic Leukemia or Pancreatic Adenocarcinoma

The analysis shows the extended circulation time of eryaspase, provides information on patient factors that influence the exposure of eryaspase, and evaluates patient population (pancreatic cancer vs ALL) and formulation (native vs recombinant asparaginase). Specifically, the simulations demonstrate that 100 U/kg dosed every two weeks would achieve the clinical AEA target levels of 100 U/L at trough in approximately 95% of patients.

The abstract (#2799) can be found at: View Source

Webcast Details

ERYTECH will hold a webcast later today, Monday, December 7, at 4:00 pm CET / 10:00am ET.

Dr. Birgitte Klug Albertsen, Associate Professor at Aarhus University Hospital, Denmark, and Principal Investigator of the trial, Dr. Iman El-Hariry, Chief Medical Officier of ERYTECH Pharma, and Gil Beyen, Chief Executive Officer of ERYTECH Pharma, will comment on the data and be available for Q&A.

The webcast can be followed live online via the link: View Source

Conference ID#: 2272914#

About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that is the most common type of cancer in children in the US and Europe. More than 13,000 cases are diagnosed in the US and Europe each year with the majority of patients diagnosed before age 20. Asparaginase has been an integral component of ALL treatment for several years but is associated with treatment-limiting hypersensitivity in up to 30% of patients. Discontinuation of asparaginase therapy in ALL patients has been associated with inferior event free survival highlighting the need for additional asparaginase based treatment options.

On December 6, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, reported preclinical findings of ALLO-316, an AlloCAR T therapy targeting CD70, in models of acute myeloid leukemia (AML) (Press release, Allogene, DEC 6, 2020, View Source [SID1234572473]). Data were presented in a poster session today at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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The Company also announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a Phase 1 trial of ALLO-316 for patients with advanced or metastatic clear cell renal cell carcinoma (RCC). The Company’s first solid tumor trial is expected to begin enrolling patients in 2021.

"We are very excited about the potential of ALLO-316, our fourth AlloCAR T investigational therapy, to treat patients with CD70 expressing malignancies across both hematologic and solid tumor indications," said Rafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. "These preclinical results in AML, coupled with previous findings of ALLO-316 in RCC presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in 2019, reinforce our belief that CD70 may become one of the more important targets across a broad spectrum of cancers."

CD70 is expressed in a number of malignancies ranging from solid tumors such as RCC, lung cancer and glioblastoma to hematologic cancers including AML, diffuse large B-cell lymphoma, multiple myeloma, and chronic lymphocytic leukemia.

In the preclinical studies presented at ASH (Free ASH Whitepaper), CD70 expression was detected on AML cell lines and primary AML samples from patients. No expression of CD70 was identified in hematopoietic stem cells. ALLO-316 demonstrated the ability to mediate efficient killing of leukemic cells in multiple models. This killing activity was specific to CD70 expression on the target cells as ALLO-316 did not kill AML cell lines in which CD70 was knocked out. The preclinical studies also showed that ALLO-316 can mask CD70 on the surface of CAR T cells thereby preventing fratercide and allowing scaled manufacturing of AlloCAR T cells.

On December 6, 2020 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate update event held on Sunday, December 6th, in conjunction with participation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Aptose Biosciences, DEC 6, 2020, View Source [SID1234572343]). The Aptose management team reviewed the current clinical status of CG-806, Aptose’s oral, first-in-class FLT3 and BTK cluster selective kinase inhibitor currently in two Phase 1 a/b trials, one trial in patients with relapsed or refractory acute myeloid leukemia (AML), and the other trial in patients with relapsed or refractory B cell malignancies; and the team also reviewed the clinical status of APTO-253, a first-in-class small molecule MYC inhibitor in a Phase 1 a/b trial in patients with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS).

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The webcast of the presentation is available on Aptose’s website here.

Aptose provided a recap on CG-806 and included the following key highlights:

B-cell malignancy trial

Increasing plasma exposure with increased dose levels, with sustained steady state concentration (trough level) above 2M in the latest cohort (750mg)
Progressive accrual of leading indicators of pharmacologic and clinical activity to date, including robust inhibition of multiple key oncogenic target pathways (including BTK) on target lymphocytosis in classic CLL patients, and modest tumor reductions in different tumor types
Latest cohort (750mg) currently under expansion following a possibly drug-related DLT, however subsequent data and analyses suggest this event is unlikely related to study drug
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Based on clinical observations to date, study enrollment now focused on certain types of CLL patients
AML trial

Initiated dosing with 450mg BID as potentially active dose based on target engagement analyses
Rapidly enrolled four patients on study drug, including both FLT3-ITD and FLT3-WT
Initial PK data consistent with exposures observed with 450mg dose level in CLL/NHL patients
Observed potential anti-leukemic activity in one heavily pretreated FLT3+ AML patient, including reduction in the percentage of peripheral blood blast count from 93% to 10% in cycle one
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Aptose also reviewed the current status of APTO-253:

Continued favorable safety and tolerability in heavily pretreated patients with relapsed or refractory AML and MDS
Continued dose-related exposure, with sustained active drug species in the 2-3µM range at the fourth dose level of 100mg/m2
Observed reductions in MYC expression in PBMCs in 24 hours following dosing in most patients
Continuing dosing of patients at the fifth dose level of 150mg/m2
"The on-target lymphocytosis and modest nodal reductions we have observed in CLL patients being treated with CG-806 may be leading indicators of potential eventual responses, similar to what has been observed in the development of other successful BTK inhibitors," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We are encouraged by the continued increase in plasma exposure, and we hope the current and future dose levels will deliver formal responses to these deeply relapsed or refractory CLL patients. In AML, we are pleased by the observation of an anti-leukemic blast reduction from 93% to 10% in one of our first patients who was heavily pretreated with several consecutive FLT3 inhibitors. For APTO-253, we continue to escalate the dose and observe MYC repression, suggesting future potential for broad anti-cancer activity. We are pleased by such indicators of activity from both CG-806 and APTO-253, and we look forward to providing further updates in the first half of 2021 and at the Annual EHA (Free EHA Whitepaper) Meeting 2021."

In addition, early clinical data, along with certain preclinical data for CG-806 and APTO-253, were presented at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The posters are now available on the presentations page of Aptose website here.