On September 7, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Commission (EC) has approved a variation to the marketing authorisation for IMBRUVICA (ibrutinib), extending the approved indication in chronic lymphocytic leukaemia (CLL) to include combination with rituximab for previously untreated adult patients (Press release, Johnson & Johnson, SEP 7, 2020, View Source [SID1234564703]). The decision is based on data from the Phase 3 E1912 study that showed previously untreated patients aged 70 years or younger treated with ibrutinib plus rituximab lived longer without disease progression than those treated with the established chemo-immunotherapy regimen fludarabine, cyclophosphamide and rituximab (FCR).2,3 The study was designed and conducted in the United States (U.S.) by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), which is part of the U.S. National Institutes of Health.2,3

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The study evaluated 529 previously untreated patients with CLL aged 70 years or younger (median age, 58 years) who were randomly assigned to receive six cycles of ibrutinib plus rituximab (IR) (n=354), followed by ibrutinib until disease progression or unacceptable toxicity, or six cycles of FCR (n=175).2

At a median follow-up of 37 months, patients treated with IR lived longer without disease progression, with a progression-free survival (PFS) rate of 88 percent, compared to 75 percent for patients treated with FCR (hazard ratio [HR] 0.34; 95% confidence interval [CI], 0.22-0.52; p<0.0001).1 The study also showed an overall survival (OS) advantage for patients treated with the IR regimen.1 The primary study results were published previously in The New England Journal of Medicine, and with extended 48-month follow-up, as presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the initial treatment benefit is maintained.2,3

"Historically, chemotherapy with FCR has been the standard of care, or first treatment prescribed for patients with previously untreated CLL," said John Gribben, MD DSc, Professor of Medical Oncology at St Bartholomew’s Hospital, Barts Cancer Institute, Queen Mary, University of London. "This decision by the EC is an important step in being able to offer patients with CLL a non-chemotherapy option in the frontline setting, building on the established efficacy and safety we have come to expect from ibrutinib-based therapy."

"We are delighted with the EC’s decision approving the use of ibrutinib in combination with rituximab for these patients," said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. "This new non-chemotherapy combination regimen can offer extended remission, as well as fewer chemotherapy-related side effects for patients living with CLL."

Adverse events for the IR arm were consistent with the known safety profiles for ibrutinib and rituximab.1 The most common adverse reactions seen with ibrutinib include diarrhoea, neutropaenia, musculoskeletal pain, rash, haemorrhage (e.g., bruising), thrombocytopenia, nausea, pyrexia, arthralgia, and upper respiratory tract infection.4 The most common serious adverse reactions (which may affect more than 1 in 20 people) include neutropenia, lymphocytosis, thrombocytopenia, pneumonia, and hypertension.4

"Ibrutinib is the most comprehensively studied Bruton’s tyrosine kinase (BTK) inhibitor with the longest follow-up across eight positive Phase 3 trials in CLL to date, and is recognised as an important advancement in treatment for patients with CLL," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "This latest milestone highlights our commitment to studying the full potential of ibrutinib and in developing regimens which can transform what a CLL diagnosis means for patients going forward."

This announcement comes after the U.S. Food and Drug Administration’s (FDA) approval of this expanded indication for ibrutinib in April 2020.

About ibrutinib
Ibrutinib is a once-a-day, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally.4 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.6

Indications for which ibrutinib is approved in Europe include:4

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 99 countries for at least one indication, and to date, has been used to treat more than 200,000 patients worldwide.7

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.8 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.9 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.10

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

On September 7, 2020 THERADIAG (ISIN: FR0004197747, Ticker: ALTER), a company specializing in in vitro diagnostics of autoimmune diseases and Theranostics reported that it will publish its consolidated half-year results closed on June 30, 2020 and approved by the Board of Directors on September 17, 2020, Monday September 21, 2020 at 5:45 p.m. CEST (Paris time) (Press release, Theradiag, SEP 7, 2020, View Source [SID1234564701]).

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Bertrand de Castelnau, Chief Executive Officer, will present these half-year results during a conference call on Tuesday, September 22, 2020, at 9:00 a.m. Paris time, and will answer questions from analysts and investors.

To access the conference call , please dial 01.72.72.74.03, followed
by the access code 24 52 93 51 #. To access the slideshow by internet , click on the following link: https: //www.anywhereconference.comConference=418950313&PIN=24529351&UserAudioMode=DATA .

The presentation will also be made available on the company’s website: View Source

The replay will also be available for a period of 90 days by dialing: 01 70 71 01 60 followed by the access code: 41 89 50 313 # then follow the instructions.

Next financial event in which Theradiag is participating:

-1 st October 2020: Seminar Health / Biotech – Portzamparc BNP Paribas Digital Format

On September 7, 2020 ImmuPharma reported that admission of the Placing Shares issued in the Placing (as defined in the announcement of 2 September 2020) which was expected to take place at 8.00am on or around 7 September 2020 is now expected to take place at 8.00 am on Tuesday 8 September (Press release, ImmuPharma, SEP 7, 2020, View Source [SID1234564687]). The Company also announces it has varied the terms of its Sharing Agreements with Lanstead Capital Investors L.P. ("Lanstead").

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On 11 June 2020, the Company announced strategic investments from L1 Capital Global Opportunities Master Fund ("L1") and Lind Global Macro Fund, managed by The Lind Partners ("Lind") comprising an issue of unsecured convertible securities and associated options (the "L1 and Lind Securities").

Following the announcement of the Placing, the Company announced on 3 September 2020 that L1 had converted $150,000 (plus accrued but unpaid interest) of their convertible security at a conversion price of 11p per share (the "Conversion").

The Company has previously undertaken with Lanstead two Subscriptions (and related sharing agreements ("Sharing Agreements") of £2.66m and £1.3m which were announced on 26 June 2019 and 30 March 2020 respectively). Summary details of the respective Sharing Agreements relating to these Subscriptions are set out below.

As a consequence of the L1 and Lind Securities, discussions have been held with Lanstead as to whether this resulted in the Benchmark Price referred to in the Sharing Agreements being increased from 13.3333 pence. Having taken legal advice, and after consultation with Lanstead, it has been agreed to vary the Sharing Agreements Benchmark Price to 20 pence whilst confirming that the Benchmark Price will not change again as a result of the arrangements with L1 and Lind unless (i) the conversion price in respect of the L1 and Lind convertible securities or the option exercise price in respect of the associated options is adjusted downwards below 11 pence or (ii) the principal amount of the convertible securities or (save in respect of any capital adjustment as envisaged by the Sharing Agreements) the number of shares subject to the options are increased (or any other modification or adjustment to or under the convertible securities that has a comparable effect to any of the foregoing).

Notwithstanding the increase in the Benchmark Price, the Company confirms the statement made in the announcement of 2 September 2020 that:

"taking into account existing cash resources and the expected net proceeds, the Company expects to have sufficient cash resources to fund operations through the end of 2023."

Receipts under the Sharing Agreements to date

In relation to the 26 June 2019 Sharing Agreement, the Company has to date received £1.315 million following 11 monthly settlements. This has resulted in the Company receiving a total of £97,000 in additional proceeds compared to the Benchmark Price of 13.3333 pence. 13 monthly settlements remain outstanding on this Sharing Agreement.

In relation to the 30 March 2020 Sharing Agreement, the Company has to date received £0.117 million following 2 monthly settlements. This has resulted in the Company receiving a total of £9,000 in additional proceeds compared to the Benchmark Price of 13.3333 pence. 22 monthly settlements remain outstanding on this Sharing Agreement.

There is no change or adjustment to the monthly settlements already received by the Company as a result of the increase of the Benchmark Price from 13.3333 pence to 20 pence. The Benchmark Price of 20p only applies to the future 13 and 22 monthly settlements under the respective Sharing Agreements.

Effect of increase in Benchmark Price

The effect of the increase in the Benchmark Price from 13.3333 pence to 20 pence is that the Company will receive less funds in future under the Sharing Agreements compared to the situation if the Benchmark Price had remained at 13.3333 pence.

The actual amount of the total proceeds under the Sharing Agreements is not determined until the full 24 months of each Sharing Agreement has completed, as each monthly settlement is determined by reference of the Benchmark Price to the measured share price (the "Measured Price") which is calculated as the average volume weighted share price ("VWAP") of the Company’s Ordinary Shares over a 20 day period prior to the monthly settlement date. (Examples are shown further below).

Notwithstanding, that to date (due to the fact that on an accumulative basis, the Measured Price has exceeded the Benchmark Price) the Company has received a total of £106,000 in additional proceeds under the Sharing Agreements, the Company’s forward looking working capital forecasts have been modelled assuming that the Measured Price and Benchmark Price are the same.

Using the same assumption that for all of the remaining months covered by the Sharing Agreements, the Measured Price is 13.3333 pence and the new Benchmark Price is 20 pence this would result in the Company receiving c£1.3m less proceeds over the period.

Related Party Transaction

Lanstead is a substantial shareholder in the Company and is interested in 26,628,573 Ordinary Shares (representing 14.55% of the current issued share capital before the admission of the Placing Shares). As such Lanstead is a related party under the AIM Rules for Companies and the variation to the terms of the Lanstead Sharing Agreements constitutes a related party transaction.

The Directors of the Company (all of whom are independent of Lanstead), having consulted with SPARK Advisory Partners, the Company’s nominated adviser, consider that the variation to the terms of the Lanstead Sharing Agreements are fair and reasonable insofar as Shareholders are concerned.

On September 7, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the United States (US) Food and Drug Administration (FDA) has approved Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test (Press release, Hoffmann-La Roche, SEP 7, 2020, View Source [SID1234564677]). This indication was approved under the FDA’s Accelerated Approval programme, based on data from the phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations. It is jointly commercialised by Genentech, a wholly owned member of the Roche Group, and Blueprint Medicines in the US and will be commercialised by Roche outside of the US, excluding Greater China*.

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"The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We remain committed to finding personalised treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumour types."

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer (MTC), and treatment options that selectively target these genetic alterations are limited. In NSCLC, RET fusions represent approximately 1-2% of patients.1 Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with Gavreto.

The approval is based on the results from the phase I/II ARROW study, in which Gavreto produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement.2 Gavreto demonstrated an overall response rate (ORR) of 57% (95% CI: 46%, 68%) and complete response (CR) rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response (DoR) was not reached (95% CI: 15.2 months, not reached).2 In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI: 50%, 86%), with an 11% CR rate.2 The most common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).2

Gavreto is now the sixth FDA-approved medicine in Roche’s portfolio of treatments for lung cancer. The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer, and is expected to make a decision on approval by 28 February 2021. This New Drug Application (NDA) was accepted for review under the FDA’s Real-Time Oncology Review (RTOR) pilot programme, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

About the ARROW study3
ARROW (NCT03037385) is a phase I/II, open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Gavreto, administered orally in people with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer (MTC), RET fusion-positive thyroid cancer and other RET-altered solid tumours. The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in people treated with 400 mg of Gavreto, once-daily. ARROW is being conducted at multiple sites across the United States, European Union and Asia.

About Gavreto
Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations, regardless of the tissue of origin. Preclinical data have shown that Gavreto inhibits primary RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment. Blueprint Medicines and Roche are also co-developing Gavreto for the treatment of patients with various types of RET-altered thyroid cancers and other solid tumours.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On September 6, 2020 ACT Genomics reported that the completion of the first closing of the latest round of equity financing from a group of strategic investors including Aflac Ventures LLC and Kyoto University Innovation Capital (Press release, ACT Genomics, SEP 6, 2020, View Source [SID1234564611]).

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"We are very pleased to have reputable strategic investors from USA and Japan participating in the first closing of our latest round of equity fund raising which will further strengthen our capital base and will provide strategic value for our business expansion in Asia and globally. New capital from this round of investment will support ACTG’s strategic plan to further expand our technology, product portfolio and global presence. Partnering with our new strategic shareholders will enable ACTG to become a global player in cancer genomic diagnostics," said Dr. Hua Chien Chen, Co-Founder and CEO of ACTG.

ACTG is a leading DNA sequencing-based cancer solution provider and transforms science into actionable solutions empowering clinicians and patients with evidence-based information to fight cancer. Company’s mission is to provide every cancer patient personalized genomic information-based treatment plans. ACTG currently has Next Generation Sequencing ("NGS") labs in Taiwan, Hong Kong and Japan. Leveraging this strategic lab footprint, it also has operations throughout Asia, catering to the unmet precision medicine needs in the local markets.