On June 22, 2020 Boehringer Ingelheim Invest GmbH ("Boehringer Ingelheim") has reported its intention to exit in full its investment in Hikma Pharmaceuticals PLC ("Hikma" or the "Company") (Press release, Hikma, JUN 22, 2020, View Source [SID1234561382]). As of today, Boehringer Ingelheim holds 40 million ordinary shares in Hikma, which represents approximately 16.4 per cent. of the issued ordinary share capital and voting rights in the Company.

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Boehringer Ingelheim has commenced an accelerated bookbuild offering (the "Bookbuild") to sell up to approximately 28 million shares in Hikma (the "Placing Shares") to institutional investors only (the "Placing"). Concurrently with the Placing, Hikma has committed to buy back from Boehringer Ingelheim such number of ordinary shares ("the Buy Back Shares") as does not exceed an aggregate value of £295 million (being an amount approximately equal to 4.99% of the aggregate market value of all the Shares of the Company at the close of business on 22nd June 2020, less the value of the commitment fee described below) (the "Buy Back"). The purchase price for each of the Buy Back Shares will be equal to the sale price for each of the Placing Shares (the "Buy Back Price"). The Buy Back Price is subject to the price limit set out below. Hikma has separately today entered into an agreement with Boehringer Ingelheim pursuant to which Hikma will receive a commitment fee of 2 per cent. of the aggregate value of the Buy Back Shares acquired at the Buy Back Price (the "Commitment Fee"). Citigroup Global Markets Limited ("Citi") will act as riskless principal for the purpose of the Buy Back.

The Buy Back is subject to the satisfaction of a number of conditions, including the successful pricing of the Placing and provided that the price payable by Hikma for the Buy Back Shares does not exceed a per share amount equal to £24.71, which, net of the 2% commitment fee, is equal to approximately £24.22, being the average closing price of the five business days preceding to today’s date. If the Placing Price is within the pricing limits that apply to the Buy Back Price, the Placing cannot proceed unless the Buy Back proceeds.

Hikma will fund the Buy Back from cash and available facilities. Hikma intends to hold the Buy Back Shares in treasury and Hikma will not receive any proceeds from the Placing. Following the successful completion of the Placing and the Buy Back, Boehringer Ingelheim would no longer hold any shares in Hikma.

The shares being sold by Boehringer Ingelheim were issued by Hikma as part of the consideration for the acquisition of Roxane Laboratories in February 2016. The Buy Back demonstrates the Board’s confidence in Hikma’s future prospects. Since its initial public offering ("IPO") in 2005, Hikma has delivered a total shareholder return of approximately 926%, exceeding the FTSE 100 total shareholder return of approximately 105%.

As at 31 December 2019, Hikma’s net debt to core EBITDA ratio was 0.4x.

Boehringer Ingelheim is a related party of Hikma for the purposes of the Listing Rules by virtue of its approximately 16.4 per cent. shareholding in Hikma. The Buy Back by Hikma and the associated payment of the Commitment Fee by Boehringer Ingelheim constitute a smaller related party transaction falling within LR 11.1.10R(1) and this announcement is therefore made in accordance with LR11.1.10R(2)(c). The aggregate amount of the Buy Back and the commitment fee cannot be higher than approximately £301 million.

Citi and Goldman Sachs International ("Goldman Sachs") are acting as joint financial advisers to Hikma on the Buy Back.

On June 22, 2020 HiFiBiO Therapeutics is presenting its three lead pipeline programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II taking place today (Press release, HiFiBiO Therapeutics, JUN 22, 2020, View Source [SID1234561300]). The company is a pioneer of novel antibody drug discovery and development leveraging single-cell analytics to treat cancer, autoimmune and infectious diseases. HiFiBiO invites members of the scientific and medical communities to listen to these poster presentations online at the AACR (Free AACR Whitepaper) meeting website or, after the AACR (Free AACR Whitepaper) meeting has concluded, at the HiFiBiO Therapeutics website.

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"These presentations demonstrate the rapid progress spearheaded by our scientists at HiFiBiO and the development of our pipeline, and we look forward to soon moving our lead programs to IND," said Liang Schweizer, PhD, President and CEO of HiFiBiO Therapeutics. "Given our depth of experience in immune modulation and cutting-edge single-cell science and technology, we believe that HiFiBiO is realizing the potential of single-cell analysis to develop novel, high-quality antibody targets into life-changing treatment options for patients."

POSTER PRESENTATION DETAILS:

Title: HFB301001, a novel OX40 agonistic antibody with a unique pharmacological profile and innovative biomarker strategy
Presenters: Andreas Raue, PhD, Project Leader, Senior Director, Head of Drug Intelligent Science (DIS) at HiFiBiO Therapeutics and Robert Petit, PhD, Senior Scientific Advisor
E-Poster: #2285
HFB301001 is being developed as a potential novel treatment option for cancer coupled with a patient stratification biomarker in solid tumor indications.

Title: Discovery and characterization of novel TNFR2 antibodies to modulate T cell activities in immunosuppressive environment
Presenters: Francisco Adrian, PhD, Senior Vice President, Head of Research and Shuo Wei, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #2282
HFB200301 is an anti-TNFR2 monoclonal antibody being developed as a potential first-in-class therapeutic for the treatment of biomarker-selected patients with advanced cancer.

Title: HFB9-2, a novel Galectin-9 neutralizing antibody to reverse immune suppression in the tumor microenvironment
Presenters: Roshan Kumar, PhD, Senior Director, Head of Discovery Biology and US External Innovation and Yun-Yueh Lu, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #6532
HFB2009 program focuses on developing anti-Gal-9 neutralizing antibodies as a potential first-in-class treatment for AML and solid tumors, both as a single agent and a combination therapy.

More information about these and other programs in the HiFiBiO Therapeutics pipeline is available at View Source

On June 22, 2020 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," "MTEM" or the "Company"), a clinical-stage biopharmaceutical company focused on the discovery and development of the Company’s proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported that four poster presentations featuring pre-clinical data on its pipeline programs are being presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting 2020, being held June 22-24, 2020 (Press release, Molecular Templates, JUN 22, 2020, View Source [SID1234561317]). Copies of the posters presented at AACR (Free AACR Whitepaper) can be found in the Presentations section of Molecular Templates’ website at View Source MTEM also announced an update on its ongoing Phase I study of MT-5111 in HER2-positive cancers.

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Poster Title: In Vivo Efficacy of a PD-L1 Targeted, Antigen Seeding Engineered Toxin Body

Authors: Hilario J. Ramos, Brigitte Brieschke, Sara LeMar, Joseph D. Dekker, Aimee Iberg, Garrett L. Robinson, Asis Sarkar, Banmeet Anand, Melissa M. Singh, Jay Zhao, Jack P. Higgins, Erin K. Willert. Molecular Templates Inc., Austin, TX
MT-6402 is a unique agent designed to deplete tumor and repressive immune cells in the tumor microenvironment. It has multiple unique mechanisms of action that may provide greater potency than is seen with current PD-L1 antibodies. MT-6402 was shown to have potent in vitro activity against a variety of PD-L1+ tumor cells and results in tumor growth delay and survival benefits in NSCLC PDX in vivo model. MT-6402 can alter the immunophenotype of the tumor and allow for recognition by effector T cells. Non-human primate (NHP) data show that MT-6402 mediated PD-L1+ immune cell clearance can elicit highly potent monotherapy immune activation in a way that has not been seen previously in NHP models with checkpoint inhibitors. MT-6402 is slated for IND filing in 2H20.

Poster Title: CTLA-4 Targeted Engineered Toxin Bodies Designed to Deplete Regulatory T Cells (Tregs)

Authors: Aimee Iberg, Edith Acquaye-Seedah, Lilia A. Rabia, Garrett L. Robinson, Hilario J. Ramos, Joseph D. Dekker, Jay Zhao, Erin K. Willert. Molecular Templates Inc., Austin, TX
Tumor resident regulatory T cells (Tregs) are important mediators of an immunosuppressive tumor microenvironment (TME) promoting tumor immune evasion. The presence of Tregs, and a higher ratio of Tregs to effector T cells in the TME, are associated with poor prognosis. There is concern that antibodies to CTLA-4 are not sufficiently effective at clearing Tregs from the TME. ETBs are being developed to specifically target CTLA-4+ Tregs and clear them from the TME. Because CTLA-4-targeted ETBs preferentially affect Tregs versus CTLA-4+ CD8 T-cells, ETBs may also have a safer profile than CTLA-4 antibodies. In co-culture models CTLA-4 ETBs were shown to relieve Treg suppression of T-effector proliferation. Experiments in mice showed that CTLA-4 ETB 1 (as labeled on the AACR (Free AACR Whitepaper) poster) displays a short serum half-life and is well tolerated in vivo. An IND for a CTLA-4 ETB is expected to be filed in 2021.

Poster Title: Novel Engineered Toxin Bodies Targeting SLAMF7 (CS1)

Authors: Aimee Iberg, Garrett L. Cornelison, Caleigh Howard, Garrett L. Robinson, Jay Zhao, Hilario J. Ramos, Erin K. Willert. Molecular Templates Inc., Austin, TX
SLAMF7 (CS1) is a clinically validated target of monoclonal antibody therapy for the treatment of multiple myeloma. The approved antibody-based therapeutic, elotuzumab, works indirectly by recruiting effector cells to the tumor but does not show single agent clinical activity. ETBs have the potential to deplete malignant cells by means of potent and direct cell kill through enzymatic ribosomal destruction. SLAMF7 ETBs were shown to be active alone and in the presence of elotuzumab. Epitopes distinct from elotuzumab are options for ETB engagement, allowing activity in the presence of elotuzumab. SLAMF7 ETBs combine with standard of care chemotherapy (IMiDs) and bortezomib in a positive manner in vitro. Lead selection is underway with the testing of various ETB scaffolds and additional binding domains targeting multiple SLAMF7 epitopes.

Poster Title: CD45 Targeted Engineered Toxin Bodies Deplete Hematopoietic and Malignant Cells

Authors: Aimee Iberg, Garrett L. Robinson, Sara LeMar, Joseph D. Dekker, Jay Zhao, Hilario J. Ramos, Melissa M. Singh, Erin K. Willert. Molecular Templates Inc., Austin, TX
CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine phosphatase. Targeted and potent ETBs with intrinsically short half-lives are being developed to specifically destroy CD45 expressing cells including malignant cells of B, T and myeloid lineage. A single agent, targeted conditioning method for bone marrow transplant (BMT), employing ETBs, has the potential to increase patient safety and eliminate genotoxic effects that are associated with existing conditioning regimens. Antibody discovery campaigns have the potential to direct ETBs to specific isoforms of CD45 for refinement of indications including various cancers and autoimmune diseases.

Update on Phase I study of MT-5111

MT-5111, a HER2 targeted ETB, is in an ongoing Phase 1 study that has two parts: Part 1 is dose escalation and Part 2 is dose expansion, which will begin when a maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) is established in Part 1. To date, 10 subjects, with a median of 5 prior lines of therapy and a median of 2 prior HER2-targeting regimens, have been treated with MT-5111 (metastatic cholangiocarcinoma n=5, metastatic breast cancer n=4, metastatic gastro-esophageal junction carcinoma n=1). Thus far, no dose limiting toxicities (DLTs) have been observed in any cohort and MT-5111 appears to be well tolerated, with no cardiotoxicity to date (cardiotoxicity is a known potential toxicity for HER2 targeted therapies).

Currently there are 4 subjects in total on treatment from the second (1 μg/kg/dose) and third cohorts (2 μg/kg/dose). No cardiac AEs or abnormalities in cardiac biomarkers have been noted thus far. Reported AEs that may be causally related among the 3 cohorts to date include the following: one instance of grade 1 chills, one instance of grade 1 hypophosphatemia, one instance of grade 1 nausea, and one instance of grade 2 AST elevation. The grade 2 AST elevation occurred in a subject in cohort 1 with disease progression in hepatic metastases; no causally related AST or ALT elevations have been noted in any other subjects to date. The ongoing subject from cohort 2 (45 y/o female with metastatic breast cancer) has stable disease (the subject only has evaluable disease but no measurable lesions per RECIST 1.1, and is classified as non-CR, non-PD per protocol) and remains on treatment, now in cycle 5. One subject in cohort 3 with metastatic breast cancer has had a follow-up CT scan at the end of cycle 2 and has stable disease. Six subjects have discontinued for disease progression and two subjects are too early to evaluate. Cohort 4 (3.0 μg/kg/dose) is anticipated to open shortly. Molecular Templates is encouraged by the safety profile to date in these heavily pretreated patients and expects to provide an update on results from the patients currently on treatment as well as higher dose cohorts from the dose escalation portion of the Phase 1 study (including doses that are predicted to be clinically active based on preclinical data) in 4Q20.

Conference Call and Webcast to Discuss AACR (Free AACR Whitepaper) Posters

Molecular Templates will host a live webcast and conference call in Eric Poma, Ph.D., Molecular Templates’ Chief Executive Officer and Scientific Officer, will provide an update on the Company’s pipeline programs and discuss the four abstracts presented at AACR (Free AACR Whitepaper).

On June 22, 2020 BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported new proof-of-concept data for two different types of monoclonal antibodies targeting tumor necrosis factor receptor 2 (TNFR2) (Press release, BioInvent, JUN 22, 2020, View Source [SID1234561333]).

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TNFR2 is particularly upregulated on tumor-associated regulatory T cells (Tregs) and has been shown to be important for their expansion and survival. As a part of its Treg program, BioInvent identified and characterized a wide panel of TNFR2-specific antibodies, generated from its proprietary n-CoDeR library and unique F.I.R.S.TTM discovery tool, of which BI-1808 and BI-1910 are the lead development candidates.

In vivo studies show that both ligand-blocking and agonistic antibodies regress large established tumors and synergize with anti-PD-1 therapy. Further mode-of-action dissection demonstrate that while the ligand-blocking antibody depleted intratumoral Tregs, the agonist increased intratumoral CD8+ T effector cells. Both antibodies expanded tumor-specific CD8+ T cells and induced long-lasting T cell memory.

Main points from the presentation included:

The two different types of TNFR2 targeting antibodies are being developed by BioInvent – BI-1808 (a ligand blocker), and BI-1910 (an agonist).
BI-1808 and BI-1910 act through differential targeting of intratumoral Tregs and CD8+ T cells to regress large inflamed tumors and sensitize the host to anti-PD-1 therapy.
Treatment with both antibodies result in an increase in numbers and activation of tumor specific T cells at the tumor site.
Martin Welschof, CEO of BioInvent, says: "The proof-of-concept data presented in this poster show very exciting potential for these two TNFR2 antibodies in improving treatment for solid cancers, and are further reinforcement of the productivity of BioInvent’s technology platform. This provides a foundation for further development and we look forward to investigating these antibodies in clinical trials, with BI-1808 expected to start a Phase l study in 2020."

These promising findings are available in a poster, which can be downloaded from the BioInvent website.

Title of the poster: "Targeting TNFR2 for Cancer Immunotherapy – Ligand blocking depletors versus receptor agonists"
Authors: Linda Mårtensson, Kirstie Cleary, Monika Semmrich, Mathilda Kovacek, Petra Holmkvist, Carolin Svensson, Mimoza Demiri, Therese Blidberg, Ulla-Carin Thornberg, Vincentiu Pitic, Osman Dadas, Sean H Lim, Stephen A Beers, Mark S Cragg, Björn Frendéus, Ingrid Teige
Session Date: June 22-24, 2020
Poster Session Title: Immune Checkpoints 1
Poster Number: 936 // Abstract Number: 5892

On June 22, 2020 RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting an abstract on RGX-104, RGENIX’s lead therapy in development (Press release, Rgenix, JUN 22, 2020, View Source [SID1234561349]). RGENIX’s abstract, "Correlative analysis of pharmacokinetics and pharmacodynamics of RGX-104, a first-in-class Liver-X-Receptor (LXR) agonist, and clinical outcomes in patients with advanced solid tumors" was accepted for the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which this year was scheduled as two virtual meetings. The abstract results will be presented as a virtual poster presentation (#LB-133/7) in the Late-Breaking Research: Clinical Research 1 session on June 22, by clinical investigator Dr. Monica Mita, Co-Director, Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, who is lead author on the study.

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RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. RGX-104 inhibits tumor angiogenesis and depletes myeloid derived suppressor cells (MDSC), thereby activating cytotoxic T-lymphocytes. MDSCs are associated with resistance to both checkpoint inhibitors (CPI) and chemotherapy, providing a rationale for combination therapy with RGX-104.

For the dose escalation stage of the Phase 1 study, RGX-104 was tested as a monotherapy or in combination with either nivolumab, ipilimumab, or docetaxel in heavily pre-treated patients with refractory or relapsed solid tumors, including patients who had progression on prior checkpoint inhibitors (CPI). As outlined in the presentation, objective clinical activity was observed in all treatment arms, including the monotherapy arm, with partial responses achieved in patients with NSCLC, SCLC, melanoma, SCCHN, and endometrial cancer.

Of note, in the combination arms, a 28.6% objective response rate was observed in all evaluable patients who had previously progressed on CPI, with 4 of 14 evaluable patients achieving PRs. Responses included ongoing durable PRs – some exceeding 11 months – in CPI refractory/resistant patients whose tumors were PD-L1 low/negative.

Importantly, clinical activity across all treatment arms was associated with RGX-104 related pharmacodynamic effects, including ApoE activation, MDSC depletion, and CD8 T cell activation with associated induction of IFNγ. Robust ApoE induction was achieved with BID dosing of RGX-104 and was correlated with the magnitude of MDSC depletion. Additionally, in comparison to PD-L1 positive tumors, PD-L1 negative tumors were found to have significantly lower baseline (pre-treatment) levels of ApoE, a feature associated with higher likelihood of clinical benefit to RGX-104. The data demonstrate that MDSC depletion via ApoE induction with RGX-104 can overcome resistance to CPI or chemotherapy, resulting in durable clinical activity.

As a result, RGX-104 is being evaluated in combination with the front-line standard-of-care regimen of pembrolizumab plus carboplatin/pemetrexed in a phase 1b/2 study currently enrolling patients with advanced non-squamous non-small cell lung cancer (NSCLC) whose tumors are PD-L1 negative. RGX-104 is also being evaluated in combination with docetaxel in a phase 1b/2 expansion study that has begun enrolling patients with relapsed/refractory extensive stage small-cell lung cancer (ES-SCLC) or high grade-neuroendocrine tumors (HG-NET).

Monica Mita, M.D., principal investigator from Cedars-Sinai Medical Center and lead author and presenter of the poster, said, "These exciting results provide clinical validation of the novel MDSC-targeting mechanism of RGX-104. The durable clinical responses observed in patients who have previously progressed on checkpoint inhibitors are very promising."

Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, "We are very encouraged by the results presented today as they demonstrate that our first-in-class drug candidate RGX-104 can robustly target MDSCs, a key drug resistance mechanism, to provide durable clinical benefit to patients. The findings further strengthen the foundation for our ongoing Phase 1b/2 studies. We look forward to sharing results from these ongoing studies."