On March 25, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3-related immunotherapy treatments for cancer and autoimmune diseases, reported data from its Phase IIb AIPAC clinical trial in HER2-negative / Hormone Receptor positive (HR+) metastatic breast cancer (MBC) (Press release, Immutep, MAR 25, 2020, View Source [SID1234555945]).

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AIPAC is a multicentre, placebo-controlled, double-blind, randomised study evaluating the Company’s lead product candidate, eftilagimod alpha (efti, LAG-3Ig or IMP321) in combination with paclitaxel, a taxane standard of care chemotherapy, in 227 MBC patients to boost the T-cell immune responses against tumours.

63% of patients who received paclitaxel plus efti were progression-free at the 6-month landmark (at the end of the chemo-immunotherapy combination phase) and according to RECIST 1.1 based on blinded independent central readers (BICR). This compares favourably to 54% of patients who received paclitaxel plus placebo. The PFS data yielded an unadjusted hazard ratio (HR) of 0.93. The secondary endpoint of Overall Response Rate (ORR) increased to 48.3% in the efti group, from 38.4% in the placebo group.

Favourable results were reported in multiple predefined patient subgroups, e.g.:

patients with low monocytes count at baseline had a positive HR of 0.61 (median PFS of 5.45 vs. 7.29 months) favouring efti

patients with a more aggressive, more immunogenic luminal B type had a positive HR of 0.65 (median PFS of 5.45 vs. 7.29 months) favouring efti

patients with lower general performance status at baseline had a positive HR of 0.76 (median PFS of 6.67 vs. 7.13 months) favouring efti

The combination of efti and paclitaxel chemotherapy was overall safe and well tolerated, further building upon efti’s strong safety profile to date.

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

These results, together with consideration of the Overall Survival (OS) and the immuno-monitoring data expected to be reported later this year, could allow the Company to build a platform to commence planning for a phase III clinical trial of efti in metastatic breast carcinoma. This will include the hypotheses for the primary and secondary endpoints and the appropriate stratification for different patient subgroups. Immutep will advance its discussions with the regulatory authorities accordingly.

Immutep CSO and CMO, Dr Frederic Triebel said: "The PFS results reported from the AIPAC study in a randomised clinical setting indicate an overall trend for clinical efficacy in HR-positive metastatic breast carcinoma, which is not a particularly immunogenic tumor and very interesting results in some meaningful subgroups. We would like to thank the patients and their families, along with the investigators for participating in this important study."

Immutep CEO, Marc Voigt stated: "We are pleased to see a clinical benefit for patients receiving efti in HR-positive metastatic breast carcinoma in multiple patient subgroups. This is just one of the four advanced solid tumor indications targeted in our efti clinical development program. We are pleased to see an efficacy trend and will carefully assess the data for further development of efti given our positive data in patient subgroups. More AIPAC results should become available in the coming months, including immuno-monitoring data and Overall Survival data."

"Another piece of evidence for efti efficacy in cancer patients comes from the interim results we are seeing from our ongoing phase II TACTI-002 trial of efti. In TACTI-002, 47% of first line non-small cell lung cancer patients responding to the combination treatment of efti with pembrolizumab, an anti-PD-1 therapy. These results are remarkable given that usually only 20% of patients respond to pembrolizumab monotherapy in this PDL-1 all comer trial indication."

AIPAC Principal Investigator, Hans Wildiers of University Hospitals Leuven, Leuven, Belgium, said: "I am pleased to see this innovative chemo-immunotherapy approach in AIPAC is well tolerated by patients, while showing a numerically (non-significant) higher progression free survival rate compared to chemotherapy alone. Hormone receptor positive breast tumours represent the majority of metastatic breast cancer patients and any active well tolerated adjunct to the weekly paclitaxel standard of care regimen, is desirable. This combination warrants further investigation in larger and more biomarker selected populations."

Further Reporting from AIPAC

The Company expects to present these clinical results in more detail at an upcoming conference. Patients are continuing in the follow up phase of the study enabling OS data to be collected. Immutep expects to report OS data in late-2020.

Webcast Details

Immutep will present this AIPAC data in a global webcast, details are as follows:

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Date & Time: Thursday, March 26th, 8am Australian Eastern Daylight Time / Wednesday, March 25th, 5pm US Eastern Daylight Time
Register: Interested parties can register via a link to the webcast on the Company’s website or via the following link: View Source
Questions: Investors are invited to submit questions in advance via [email protected].
A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the AIPAC trial

Active Immunotherapy PAClitaxel (AIPAC) is a Phase IIb clinical trial in HER2-negative/ HR positive metastatic breast cancer. Based on Immutep’s LAG-3 technology, the study evaluates the combination of the Company’s lead product candidate, eftilagimod alpha (efti, LAG-3Ig or IMP321), and a taxane chemotherapy, called paclitaxel, as an immunotherapy. This combination is aimed at boosting the immune response against tumour cells compared to chemotherapy alone. In AIPAC, 227 hormone receptor positive metastatic breast cancer patients are randomised 1:1 to treatment A (paclitaxel chemotherapy plus placebo) or treatment B (paclitaxel chemotherapy plus eftilagimod alpha) for six months.

Patients receive weekly paclitaxel at Days 1, 8 and 15 with either efti of placebo injected subcutaneously, on Days 2 and 16 of each 4-week cycle, repeated for 6 cycles. Thereafter, patients pass over to the maintenance phase with efti alone.

The primary end point is to determine progression-free survival (PFS) and key secondary objectives include overall survival, safety, quality of life and objective response rate.

For more information regarding the AIPAC trial, visit clinicaltrials.gov (identifier NCT02614833) and View Source).

On March 25, 2020 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported that it will report financial results for the year ended December 31, 2019 and host a conference call on Friday, March 27, 2020 (Press release, Altimmune, MAR 25, 2020, View Source [SID1234555878]).

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Conference Call Details
Date: Friday, March 27
Time: 8:30 am Eastern Time
Domestic: 877-423-9813
International: 201-689-8573
Conference ID: 13701071
Webcast: View Source

On March 25, 2020 LIDDS AB (publ) reported preclinical studies using a TLR9 agonist formulated with NanoZolid (NZ-TLR9) showing that a single NZ-TLR9 injection is reducing tumor growth and improves the survival rate (Press release, Lidds, MAR 25, 2020, View Source [SID1234555853]). The in vivo efficacy is as good as with repeated injections of the standard TLR9 agonist. The pharmacokinetic analysis of treated tumors has confirmed the depot function of NZ-TLR9.

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Clinical data have shown that intratumoral delivery of TLR9 agonists can effectively treat solid cancers. The NanoZolid technology can provide sustained intratumoral release of the injected TLR9 agonist, minimize the need for repeated injections, and allow for a safer treatment of deep-lying tumors. LIDDS preclinical trials in a syngeneic mouse model where LIDDS NZ-TLR9 was intratumorally injected with the NanoZolid technology shows that the antitumoral immune responses were enhanced as well as showing strong antitumoral efficacy data. Importantly, NZ-TLR9 injection is similar in antitumoral efficacy as repeated injections with a standard non-formulated TLR9 agonist.

-TLR9 is one of the most promising immunotherapy targets with a great potential both as monotherapy and in combination with other therapies such as checkpoint inhibitors. The NanoZolid technology addresses key issues in developing TLR agonists as repeated intratumoral injections are needed using standard formulations, said Monica Wallter, CEO of LIDDS.

A preclinical programme is ongoing to further deepen the data obtained so far and LIDDS is preparing for a phase I clinical trial using NanoZolid combined with a TLR9 agonist. The first human study is planned to start in 2021.

To increase antitumoral efficacy and avoid severe systemic side effects, TLR9 agonists are predominantly given as intratumoral injections. However, the need for repeated intratumoral injections when using standard formulated TLR9 agonists poses a risk for the patients and increases the costs for the healthcare systems. The NanoZolid technology having a longer and controlled drug substance release is suitable for a TLR9 agonist treatment, enabling a potential reduction in number of injections and patient compliance.

-I’m really proud of the LIDDS team that successfully have developed a NanoZolid controlled-release formulation of a TLR9 agonist. There is significant commercial potential in this area of research and drug development and the market for TLR agonists is expected to be worth hundreds of millions of dollars over the coming years, commented Monica Wallter.

On March 25, 2020,Thermo Fisher Scientific Inc. (the "Company") reported that it has issued $1,100,000,000 aggregate principal amount of 4.133% Senior Notes due 2025 (the "2025 Notes") and $1,100,000,000 aggregate principal amount of 4.497% Senior Notes due 2030 (the "2030 Notes" and, together with the 2025 Notes, the "Notes") in a public offering (the "Offering") pursuant to a registration statement on Form S-3 (File No. 333-229951) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Notes, each as previously filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, Thermo Fisher Scientific, MAR 25, 2020, View Source [SID1234555849]).

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The Notes were issued under an indenture, dated as of November 20, 2009 (the "Base Indenture"), and the Twentieth Supplemental Indenture, dated as of March 25, 2020 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), between the Company, as issuer, and The Bank of New York Mellon Trust Company, N.A., as trustee. The sale of the Notes was made pursuant to the terms of an Underwriting Agreement, which the Company entered into on March 23, 2020 (the "Underwriting Agreement"), with J.P. Morgan Securities LLC, Morgan Stanley & Co. LLC, BofA Securities, Inc., Deutsche Bank Securities Inc. and Mizuho Securities USA LLC, as representatives of the several underwriters named in Schedule A to the Underwriting Agreement.

The 2025 Notes will mature on March 25, 2025, and the 2030 Notes will mature on March 25, 2030. Interest on the Notes will be paid semi-annually in arrears on March 25 and September 25 each year, commencing on September 25, 2020.

Prior to February 25, 2025 in the case of the 2025 Notes (one month prior to their maturity) and December 25, 2029 in the case of the 2030 Notes (three months prior to their maturity) (each, a "Par Call Date"), the Company may redeem each series of Notes, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the Notes of such series to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes of such series being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such Notes to be redeemed matured on the Par Call Date), discounted to the date of redemption on a semi-annual basis (assuming a 360-day year of twelve 30-day months), at the Treasury Rate (as defined in the Indenture) plus, in each case, 50 basis points, plus, in each case, accrued and unpaid interest on the Notes of such series being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the applicable Par Call Date, the Company may redeem some or all of the Notes at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding the date of redemption.

Upon the occurrence of a change of control (as defined in the Indenture) of the Company and a contemporaneous downgrade of the Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings, Limited, the Company will, in certain circumstances, be required to make an offer to purchase the Notes at a price equal to 101% of the principal amount of the Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of the Company. The Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Notes. The Notes are also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries.

The Indenture contains limited affirmative and negative covenants of the Company. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The Indenture also limits the ability of the Company to merge or consolidate or sell all or substantially all of its assets.

Upon the occurrence of an event of default under the Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of the Company under the Notes may be accelerated, in which case the entire principal amount of the Notes would be immediately due and payable.

The Company expects that the net proceeds from the Offering will be approximately $2.18 billion, after deducting the underwriting discount and estimated offering expenses. The Company intends to use the net proceeds of the offerings (together with cash on hand) to pay a portion of the consideration for the previously announced acquisition of QIAGEN N.V., a public limited liability company organized under the laws of The Netherlands ("QIAGEN"), including the repayment of indebtedness of QIAGEN, and for general corporate purposes.

On March 25, 2020 ArcherDX, Inc., reported that its ArcherMET companion diagnostic (CDx) has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceutical Medical Devices Agency (PMDA) to detect MET exon 14 (METex14) skipping alterations in tissue (RNA) and liquid biopsy (ctDNA) from patients with advanced non-small cell lung cancer (NSCLC) for consideration for treatment with Merck KGaA, Darmstadt, Germany’s oral MET inhibitor, TEPMETKO* (tepotinib) (Press release, ArcherDX, MAR 25, 2020, https://www.prnewswire.com/news-releases/archerdx-receives-approval-for-archermet-companion-diagnostic-for-tepmetko-tepotinib-in-advanced-non-small-cell-lung-cancer-in-japan-301029535.html [SID1234555838]). ArcherMET is the first and only CDx to be approved for the detection of MET gene alterations and it allows for testing of blood and tissue samples. TEPMETKO is the first approved MET inhibitor in Japan, and is indicated for the treatment of unresectable, advanced or recurrent non-small cell lung cancer with METex14 skipping alterations. TEPMETKO is administered orally once daily. Please see recent news about TEPMETKO here.

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Merck KGaA, Darmstadt, Germany launched a strategic partnership with ArcherDX in 2018 to develop a CDx featuring both liquid and tissue biopsy capabilities, including a program to identify METex14 skipping alterations among patients with advanced NSCLC.

"We’re delighted that the Japan approval of ArcherMET as a companion diagnostic for TEPMETKO means NSCLC patients will have access to Merck KGaA, Darmstadt, Germany’s targeted therapy with demonstrated efficacy," said Jason Myers, Ph.D., Chief Executive Officer and co-founder, ArcherDX. "This approval is the most recent highlight from our ongoing partnership with Merck KGaA, Darmstadt, Germany, and demonstrates our ability to deliver highly accurate and precise companion diagnostics that enable our global partners to accelerate access to therapies for patients in need and democratize personalized medicine."

"With the approval of TEPMETKO and its companion diagnostic, ArcherMET in Japan, NSCLC patients harboring MET exon 14 skipping alterations can now be identified and treated with a targeted approach and precision that was not previously possible," said Zhen Su, M.D., MBA, Senior Vice President & Head of Global Franchise Oncology, Merck KGaA, Darmstadt, Germany. "We are excited that through our partnership with ArcherDX, we are able to address this unmet medical need with a precision approach and deliver important progress for patients living with this aggressive form of lung cancer."

Lung cancer is one of the most common types of cancer worldwide, with approximately 2 million cases diagnosed in 2018.i It is also the second most common type of cancer in Japan. Alterations of the MET signaling pathway, such as METex14 skipping alterations, are found in various cancer types, including 3% to 5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis.ii,iii,iv

*The brand name TEPMETKO is not approved for use outside of Japan.