On March 30, 2021 InDex Pharmaceuticals Holding AB (publ) reported that the company has entered an agreement for services with global clinical research organization (CRO) Parexel Biotech for the phase III study CONCLUDE(Press release, InDex Pharmaceuticals, MAR 30, 2021, View Source [SID1234584071]). The study will evaluate the efficacy and safety of the drug candidate cobitolimod for the treatment of moderate to severe left-sided ulcerative colitis.

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"We are excited to advance cobitolimod into phase III, which is the final stage of development before application for market approval. After the successful collaboration in our recent phase IIb study CONDUCT, we are very pleased to collaborate once again with Parexel Biotech as our clinical development partner", says Peter Zerhouni, CEO of InDex Pharmaceuticals. "Parexel Biotech is a leading global CRO with considerable experience managing phase III studies in inflammatory bowel disease, which will ensure an efficient execution of the study."

CONCLUDE is a randomised, double-blind, placebo-controlled, global phase III study to evaluate cobitolimod as a novel treatment for patients with moderate to severe left-sided ulcerative colitis. The induction study will include approximately 400 patients, and the primary endpoint will be clinical remission at week 6. Patients responding to cobitolimod in the induction study will be eligible to continue in a one-year maintenance study, where they will be treated with either cobitolimod or placebo.

Apart from the dosing 250 mg x 2, which was the highest dose and the one that showed the best efficacy in the phase IIb study CONDUCT, the phase III study will also evaluate a higher dose, 500 mg x 2, in an adaptive study design. This higher dose has the potential to provide an even better efficacy than what was observed in the phase IIb study.

"We are pleased to partner with InDex Pharmaceuticals on the phase III clinical trial CONCLUDE to evaluate a potential new therapy for patients with moderate to severe ulcerative colitis," said Jim Anthony, Senior Vice President and Global Head, Parexel Biotech. "Our collaboration with InDex Pharmaceuticals demonstrates our commitment to designing innovative solutions that draw from our global clinical experience and therapeutic expertise to fulfill unmet medical needs on behalf of patients worldwide."

For more information:
Peter Zerhouni, CEO
Phone: +46 8 122 038 50
E-mail: [email protected]

Publication
The information was submitted for publication through the agency of the contact person set out above at 8:00 CET on March 30, 2021.

Cobitolimod in brief
Cobitolimod is a first-in-class Toll-like receptor 9 (TLR9) agonist that can provide an anti‐inflammatory effect locally in the large intestine, which may induce mucosal healing and relief of the clinical symptoms in ulcerative colitis. Cobitolimod met the primary endpoint in the phase IIb study CONDUCT and demonstrated an outstanding combination of efficacy and safety. The results were recently published in the reputable medical journal, The Lancet Gastroenterology & Hepatology. Data from four previous completed placebo-controlled clinical trials support the efficacy and safety demonstrated in the CONDUCT study.

On March 30, 2021 Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported the publication of a peer-reviewed paper entitled, "Development of a CD8 co-receptor independent T cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy" covering preclinical research on a T cell receptor (TCR) specific for a peptide derived from the MAGE-A4 protein in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, MediGene, MAR 30, 2021, View Source [SID1234577444]). The research was conducted by Medigene’s scientists in collaboration with scientists from bluebird bio, Inc. (bluebird bio, NASDAQ: BLUE). The paper was published online: View Source

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The paper describes the discovery and characterization of a MAGE-A4-specific TCR and provides detailed scientific information highlighting the robust potency and exquisite specificity of this TCR against a MAGE-A4-derived peptide.

This MAGE-A4-specific TCR is the most advanced program in Medigene’s collaboration with bluebird bio. This TCR differs from other MAGE-A4 TCRs currently in development elsewhere as it works independently of the T cell co-receptor CD8, which is found on killer T cells. As shown in the paper, this enables T cells equipped with this MAGE-A4 TCR to detect and kill tumor cells expressing MAGE-A4 in a preclinical setting, including helper T cells which express CD4 and not CD8.

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: "We are delighted to see the high quality of our collaborative research with bluebird bio recognized by this scientific publication. This MAGE-A4-specific TCR, being CD8 co-receptor independent, can activate MAGE-A4-specific responses in either CD4 helper or CD8 killer T cells. In this way, the TCR enables the broadest functional T cell response against MAGE-A4-positive tumor cells and, as demonstrated in preclinical in vivo models, strong control of tumor growth.
Our allogeneic T cell priming, and selection technology was used very successfully to isolate this TCR. This technology is well suited to finding such non-mutated, high avidity TCRs specific for different antigens which we believe will be key to developing next generation TCR-T cells for solid cancer."

Scientific Information
The MAGE-A4-specific HLA-A2-restricted TCR was isolated using Medigene’s allogeneic priming technology to stimulate and screen T cells from an HLA-A2-negative donor for cells with the desired specificity. In preclinical research, the TCR has a favorable activity profile and superior in vivo potency compared to other specific MAGE-A4 TCRs tested (including those isolated from HLA-A2-positive donors who have tolerized T cell repertoires to self-antigens presented by HLA-A2). This non-mutated, high avidity MAGE-A4-specific TCR is CD8 co-receptor-independent, allowing effector functions to be elicited in CD4 helper T cells transduced to express the TCR. These CD4 TCR-T cells not only supported an anti-tumor response by direct killing of MAGE-A4-positive tumor cells, but also upregulated certain properties associated with helper function, such as surface marker expression and release of key cytokines.

On March 30, 2021 LONDON, Silence Therapeutics plc, AIM: SLN and Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported its audited full year results for the year ended 31 December 2020 (Press release, Silence Therapeutics, MAR 30, 2021, View Source [SID1234577429]).

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Mark Rothera, President and CEO of Silence Therapeutics, commented: "2020 was a transformational year for Silence Therapeutics, driven by the remarkable resilience of our people in what was a challenging year for the world. We have made significant progress with our mRNAi GOLD platform, with both lead programmes now in the clinic and three data readouts due this year. Alongside advancing our wholly owned pipeline, we continue to progress our high-value partnerships and through this two-pronged approach, our goal is to deliver 2-3 INDs per year from 2023. We are well positioned for success and motivated by our vision to transform people’s lives through our precision engineered medicines."

Craig Tooman, CFO of Silence Therapeutics, commented: "Silence ended 2020 in a strong financial position, driven by non-dilutive funding from our collaborations. Our balance sheet has been further strengthened by the recent $45 million financing, which demonstrated the growing appreciation for Silence and expanded our global shareholder base. We will look to build upon this in 2021 as we continue to enhance our capabilities and maximise the opportunity of our mRNAi GOLD platform."

Operational Highlights

Advanced both wholly owned product candidates, SLN360 for cardiovascular disease due to high Lipoprotein(a), or Lp(a) levels and SLN124 for thalassaemia and myelodysplastic syndrome (MDS).

SLN360 received approval of an initial drug application (IND) by the FDA and Silence initiated the APOLLO Phase 1 study in people with high Lp(a) levels.

SLN124 was granted rare paediatric disease designation for thalassaemia as well as orphan drug designations for MDS and thalassaemia by the FDA.

Initiated the GEMINI Phase 1 study of SLN124 in healthy volunteers.

Secured a significant collaboration deal with AstraZeneca to discover and develop siRNA therapeutics for up to 10 targets in cardiovascular, renal, metabolic and respiratory diseases.

Upfront cash payment of $20m was received and another $40m is due in the first half of 2021.

Deal economics include up to $400m in milestone payments and royalties for each programme.

Expanded RNAi collaboration with Mallinckrodt for complement-mediated diseases with Mallinckrodt exercising options to license two additional targets from Silence, bringing the total to the maximum three programmes envisaged in the collaboration deal.

Commenced a technology evaluation with Takeda to explore the potential of using Silence’s mRNAi GOLD platform against a novel, undisclosed target.

Appointed Dr Giles Campion as Executive Director, Dr Marie Wikström Lindholm as Senior Vice President, Molecular Design, Dr Eric Floyd as Senior Vice President, Head of Global Regulatory Affairs and Quality Assurance and Dr Barbara Ruskin as Senior Vice President, General Counsel and Chief Patent Officer.

Launched a Scientific Advisory Board comprising world-leading scientists and clinicians to support the optimisation of Silence’s mRNAi GOLD platform and guide development strategies for SLN360 and SLN124.

Completed U.S. listing and our American Depository Shares (ADSs) began trading on the Nasdaq Capital Market (Nasdaq) under the symbol "SLN" on 8 September 2020.

Appointed Mark Rothera as our President, Chief Executive Officer and Board member.

Financial Highlights

Cash and cash equivalents and term deposits of £37.4m at year-end (2019: £33.5m). The Group had £97.5m on a proforma basis, which includes £37.4m at year-end, plus the £29.3m ($40m) receivable from AstraZeneca due in the first half of 2021, plus net proceeds of £30.8m from the February 2021 capital raise.

Cash flow from operating activities was £10.8m outflow (2019: £1.7m inflow) against an operating loss of £35.8m (2019: £22.7m). 2020 included receipts of $20m upfront from AstraZeneca, $2.0m in milestones from Mallinckrodt Pharmaceuticals, and a $2.0m upfront from Takeda.

2020 loss was higher primarily due to increased research and development spend in relation to our SLN360 and SLN124 proprietary programmes, as well as general and administrative expenses mainly relating to the Nasdaq listing.

Post Year-end

Appointed Dr Michael H. Davidson to the Silence Board of Directors as a Non-Executive Director and Craig Tooman to the Executive Leadership Team as Chief Financial Officer.

Completed an oversubscribed $45m (c. £33m) private placement led by top-tier US institutional healthcare funds.

Initiated dosing in the APOLLO Phase 1 study of SLN360 in people with high Lp(a) levels.

Initiated work with Mallinckrodt on the third complement target which triggered a $2.0m research milestone payment to Silence.

Completed enrolment in the GEMINI Phase 1 study of SLN124 in healthy volunteers.

Initiated the GEMINI II Phase 1b study of SLN124 in people with thalassemia and MDS.

On March 30, 2021 Achilles Therapeutics plc (NASDAQ: ACHL), a clinical-stage biopharmaceutical company developing precision T cell therapies to treat solid tumors, reported the pricing of its initial public offering in the United States of 9,750,000 American Depositary Shares ("ADSs") representing 9,750,000 ordinary shares at an initial public offering price of $18.00 per ADS for total gross proceeds of $175.5 million (Press release, UCLB, MAR 30, 2021, View Source [SID1234577415]). All ADSs sold in the offering are being offered by Achilles. The ADSs are expected to begin trading on The Nasdaq Global Select Market on March 31, 2021 under the ticker symbol "ACHL." In addition, Achilles has granted the underwriters a 30-day option to purchase up to an additional 1,462,500 ADSs at the initial public offering price, less underwriting discounts and commissions. The offering is expected to close on April 6, 2021, subject to customary closing conditions.

J.P. Morgan, BofA Securities and Piper Sandler are acting as joint book-running managers for the offering. Chardan, Oppenheimer & Co, and Kempen & Co are acting as co-managers.

A registration statement relating to these securities was declared effective on March 30, 2021. The securities referred to in this announcement are to be offered only by means of a prospectus. A copy of the final prospectus, when available, may be obtained from:

J.P. Morgan Securities LLC, Attention Equity Syndicate Desk, 383 Madison Avenue, New York, New York 10179, or via email: [email protected];
BofA Securities, Attention: Prospectus Department, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, or via email: [email protected]; or
Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone: (800) 747-3924, or via email: [email protected].

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On March 30, 2021 Race Oncology Limited ("Race") reported that it has entered into a new collaborative preclinical research program with The University of Newcastle (Press release, Race Oncology, MAR 30, 2021, View Source [SID1234577414]). This work will be led by the eminent cancer researcher, Associate Professor Nikki Verrills, who successfully ran Race’s preclinical breast and ovarian program (ASX announcements: 24 November 2020, 23 February 2021, 9 March 2021).

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The aim of this project is to support the clinical use of Bisantrene as a novel treatment for extramedullary AML, a difficult to treat form of AML, using an extramedullary mouse model developed by A/Prof Verrills’ team. Extramedullary AML occurs when the leukaemia spreads from the bone marrow and forms solid tumours in tissues such as the skin, breast, kidney, brain, or other organs1. A 2020 prospective positron imaging trial identified that up to 22% of AML patients have extramedullary AML2.

In a recent Sheba Medical Centre Phase II clinical trial conducted in relapsed and refractory (R/R) AML patients (ASX announcement: 16 June 2020), Bisantrene was observed to be highly effective in patients with extramedullary AML, with all patients with this subtype (4/4) showing a clinical response3. Patients with extramedullary AML currently have limited treatment choices with no approved, and very limited experimental treatment options4.
Race is pursuing Bisantrene therapies targeting AML, as part of its Three Pillar strategy (ASX announcement: 30 Nov 2020). This new program could lead to AML treatments with improved safety and efficacy for patients with extramedullary AML.

In addition, this study will be used to provide supportive data for a pivotal (Phase II/III) trial of Bisantrene in extramedullary AML patients with the aim of providing a rapid path to FDA approval for Bisantrene as an orphan drug under the 505(b)(2) track. Orphan drug designation provides for seven years post approval marketing exclusivity in the USA and 10 years in the EU/UK, as well as other tax and regulatory benefits.

"This is a key project for Race using Associate Professor Verrills’ extramedullary AML mouse model. Recent clinical evidence has identified Bisantrene as an effective treatment option for patients with the difficult-to-treat extramedullary form of AML. We believe that we have identified a low-risk pathway to rapid approval of Bisantrene via this indication that offers significant upside for Race in a crowded clinical space."

Chief Scientific Officer, Dr Daniel Tillett
This project is to start immediately with the pre-clinical results expected to be reported over the coming 12 months.

About Associate Professor Verrills
Since completing her PhD in 2005 on chemotherapy resistance in childhood leukaemia, Associate Professor Verrills was awarded a Peter Doherty Postdoctoral Fellowship from the National Health and Medical Research Council in 2006. In the same year she was the inaugural recipient of a Hunter Medical Research Foundation grant for young cancer researchers. Since then she has established an innovative research lab at the University of Newcastle studying the differences between cancer cells that respond well to drug treatments and those that do not.

Prof Verrills is currently supported by a fellowship from the Australian Research Council and project funding from the National Health and Medical Research Council. She has published over 60 journal articles with an H-index of 24.