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Genmab Announces Initial Resolution of Its Second Arbitration Under License Agreement with Janssen

On April 21, 2023 Genmab A/S (Nasdaq: GMAB) reported an award in the second arbitration arising under its license agreement with Janssen Biotech, Inc. (Janssen) for daratumumab (Press release, Genmab, APR 21, 2023, View Source [SID1234630349]). The arbitral tribunal dismissed Genmab’s claims, on the basis that they should have been brought in the first arbitration. One of the three arbitrators dissented. Genmab has the right to seek review of the award, which it must do within a limited period of time. Genmab is currently considering its options.

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Genmab’s dismissed claims were a claim for milestone payments with respect to the subcutaneous formulation of daratumumab ("SC daratumumab," marketed as DARZALEX FASPRO in the United States) and a claim for a new 13-year royalty term, on a country-by-country basis, from the date of the first commercial sale of SC daratumumab in each such country.

In accordance with the license agreement, the arbitration was conducted before a tribunal of three arbitrators under the rules of the CPR Institute for Dispute Resolution for Non-Administered Arbitration. Genmab has the right to seek review of the award, before a single "appeal arbitrator," which it must do within a limited period of time. The award has no effect on Genmab’s financial guidance and the milestone payments are not included in our current financial guidance published on February 22, 2023.

This arbitration remains confidential, subject to the parties’ disclosure obligations under applicable law. Other than pursuant to these obligations, Genmab does not intend to comment further or to provide additional information regarding the arbitration. Genmab’s various collaborations with Janssen will continue.

Sirona Biochem Announces Close of Oversubscribed Debenture Financing

On April 20, 2023 Sirona Biochem Corp. (TSX-V: SBM) (Frankfurt: ZSB) (Xetra: ZSB) (the "Company") reported that it has closed an oversubscribed, non-brokered convertible debenture for gross proceeds of $1,563,600 (Press release, Sirona Biochem, APR 20, 2023, View Source [SID1234630387]). The private placement consists of 1,563 Debenture units, (the "Debenture Units") at a price of $1,000 per Debenture Unit.

Dr. Howard Verrico, CEO, subscribed to $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 relied 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, did not exceed 25% of the Company’s market capitalization.

"Although we are in a challenging market, I am confident the value of our platform technology will be recognized as we advance our diverse pipeline. It is my intention to support Sirona, as needed, both financially and by working with our team to make Sirona a commercial success. We appreciate the contribution of the long-term shareholders in this financing who share my vision", reports Dr. Howard Verrico.

Approximately 1/3 of the net proceeds from the Offering will be used 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).

Each Debenture Unit has 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 April 20, 2026 (the "Maturity 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 consists of one Share and one non-transferable share purchase warrant (a "Warrant"). Each Warrant is 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 Company compensated finder, PI Financial Corp. (the "Finder"), by way of cash fees of $12,500 and 125,000 warrants (the "Finder’s Warrants"). Each Finder’s Warrant entitles the
Finder to acquire common shares of the Company (each, a "Finder’s Warrant Share") at $0.15 per Finder’s Warrant Share for a period of 36 months from the date of issuance.

Termination of a Material Definitive Agreement

As previously disclosed in July 2021, Avalo Therapeutics, Inc. (the "Company"), entered into a Controlled Equity Offering Sales Agreement (the "Sales Agreement") with Cantor Fitzgerald & Co. ("Cantor") and RBC Capital Markets, LLC ("RBC", and collectively with Cantor, the "Sales Agents"), as sales agents, pursuant to which the Company may offer and sell, from time to time through the Sales Agents, shares of the Company’s common stock, par value $0.001 per share, having an aggregate offering price of up to $50.0 million (Filing, 8-K, Avalo Therapeutics, APR 20, 2023, View Source [SID1234630381]).

On April 20, 2023, the Company delivered written notice to Cantor and RBC to terminate the Sales Agreement, effective no later than April 30, 2023, pursuant to Section 12(b) of the Sales Agreement. The Company is not subject to any termination penalties related to the termination of the Sales Agreement.

The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which was filed as Exhibit 1.1 to the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on July 2, 2021 and incorporated herein by reference.

CARsgen’s CAR T-cell Candidate CT041 Achieves IND Clearance from the NMPA for the Postoperative Adjuvant Therapy of Pancreatic Cancer

On April 20, 2023 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that CT041, an autologous CAR T-cell product candidate against the protein Claudin18.2 (CLDN18.2), has achieved IND clearance from the National Medical Products Administration (NMPA) for the postoperative adjuvant therapy of CLDN18.2 positive pancreatic cancer (PC) (Press release, Carsgen Therapeutics, APR 20, 2023, View Source [SID1234630367]).

Dr Raffaele Baffa, Chief Medical Officer of CARsgen, commented that "We are glad to receive the IND clearance from NMPA for the adjuvant treatment of CLDN18.2 positive pancreatic cancer using CT041. Pancreatic cancer remains a deadly disease with a dismal prognosis and lack of effective therapies. As indicated in previous clinical trials, CT041 has shown promising efficacies in treating pancreatic cancer. With this IND clearance, we look forward to exploring the use of CT041 for the adjuvant treatment and its potential to create deeper responses for pancreatic cancer patients. Driven by the vision of ‘Making Cancer Curable’, we will continue to explore the use of our CAR T-cells in the earlier line treatment of various cancer types."

About CT041

CT041 is an autologous CAR T-cell product candidate against the protein CLDN18.2 that has the potential to be the first-in-class globally. CT041 targets the treatment of CLDN18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and PC.

Active trials in CARsgen include investigator-initiated trials, a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). In January 2022, CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma with CLDN18.2 positive tumors. In November 2021, CT041 was granted PRIME Eligibility by the EMA for the treatment of advanced gastric cancer. In 2020 and 2021, CT041 received Orphan Drug designation from the U.S. FDA for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA for the treatment of advanced gastric cancer. A Phase 2 clinical trial of CT041 in the U.S. is planned to initiate in the first half of 2023.

OSE Immunotherapeutics Presents Additional Preclinical Updates on CLEC-1, a Novel Myeloid Immune Checkpoint in Immuno-Oncology

On April 20, 2023 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported two additional posters preenting the latest research updates on CLEC-1 (new myeloid immune checkpoint), from its Myeloid platform, at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held in Orlando (Florida) on April 14-19 (Press release, OSE Immunotherapeutics, APR 20, 2023, View Source [SID1234630377]).

CLEC-1, novel myeloid immune checkpoint target

The academic collaboration conducted with Dr Elise Chiffoleau’s team at the Center for Translational Research in Transplantation and Immunology (1) has led to identify CLEC-1 as a checkpoint, a receptor expressed by myeloid cells inhibiting key pro-phagocytic and T-cell cross-priming functions and hence limiting anti-tumor immune responses.

Dr Aurore Morello, Head of Research of OSE Immunotherapeutics, comments: "Altogether, the data presented at the AACR (Free AACR Whitepaper) meeting demonstrate that CLEC-1 acts as a new immune checkpoint in myeloid cells and highlight the CLEC-1/new ligand TRIM21 axis as a new target for cancer immunotherapy. These latest data generated from our teams’ collaboration provide evidence to further support the preclinical evaluation of monoclonal antagonist antibodies targeting CLEC-1. Importantly, this opens the way for further upcoming translational clinical studies aiming at developing a new myeloid immune checkpoint therapy releasing the breaks on macrophages and dendritic cells."

"CLEC-1 inhibitory myeloid checkpoint blockade enhances antitumor responses and tumor phagocytosis by macrophages".

CLEC-1 blockade with proprietary monoclonal antibodies increases tumor rejection in monotherapy and synergizes with chemotherapy. Anti-CLEC-1 monoclonal antibodies profoundly impacted the tumor environment: frequencies of invigorated dendritic cells and macrophages, activated cells and memory T-cells were increased, while frequencies of immunosuppressive myeloid cells and PD1-expressing T-cells were largely decreased.

The findings presented also revealed a previously unrecognized function for CLEC-1 in myeloid cells as a specific sensor of non-homeostatic cell death. The data showed that the absence of CLEC-1 suppresses tumor growth and hinders immunosuppressive tumor microenvironment.

"TRIM21 is a novel endogenous partner of the inhibitory myeloid checkpoint CLEC-1 involved in tumor antigen cross-presentation".

TRIM21, an intra-cellular Fc receptor and E3 ubiquitin ligase, is identified as a novel interaction partner for CLEC-1 (a discovery published in ‘Sciences Advances’ last November: Drouin et al., 2022). The research demonstrated the functional relevance of CLEC-1 interaction with its ligand. High TRIM21 expression is predictive of worse overall survival in patients with hepatocellular carcinoma, pancreatic cancer, or glioma. Mechanistically, CLEC-1 inhibition enhances the capacity of dendritic cells to cross-present tumor antigens to T lymphocytes, a process known to be regulated by TRIM21 through its E3 ubiquitin ligase activity. Antagonist anti-CLEC-1 or anti-TRIM21 antibodies are therefore being evaluated to further confirm the involvement of the newly identified CLEC-1 interaction with TRIM21 in the regulation of CLEC-1’s function as an inhibitory myeloid checkpoint.

(1) Collaborative academic program between OSE Immunotherapeutics and Dr Elise Chiffoleau’s research teams (Center for Research in Transplantation and Translational Immunology (CR2TI), UMR1064, INSERM, Nantes University at Nantes University Hospital, View Source).

Poster presentation details:

Poster CLEC#1

Title: "CLEC-1 inhibitory myeloid checkpoint blockade enhances antitumor responses and tumor phagocytosis by macrophages""
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM
Location: Section 23
Poster Board Number: 2

Poster CLEC#2

Title: "TRIM21 is a novel endogenous partner of the inhibitory myeloid checkpoint CLEC-1 involved in tumor antigen cross-presentation"
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM
Location: Poster Section 23
Poster Board Number: 9