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 Invitae (NYSE: NVTA), a leading genetics company, and ArcherDX, a leading genomics analysis company democratizing precision oncology, reported the companies have entered into a definitive agreement under which Invitae will combine with ArcherDX to create a genetics leader with unrivaled breadth and scale in cancer genetics and precision oncology (Press release, Invitae, JUN 22, 2020, View Source [SID1234561371]).

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The combined company will be poised to transform care for cancer patients, accelerating adoption of genetics through the most comprehensive suite of products and services available. Integrating germline testing, tumor profiling and liquid biopsy technologies and services in a single platform will enable precision approaches from diagnostic testing to therapy optimization and monitoring, expanding access to best-in-class personalized oncology.

"From the beginning, Invitae’s goal has been to aggregate the world’s genetic tests into a single platform in service of our mission to bring comprehensive genetic information into mainstream medicine. Today, we take another major step forward in that effort," said Sean George, Ph.D., co-founder and chief executive officer of Invitae.

"ArcherDX and Invitae share a foundational belief in the power of genomic information to impact care. We are thrilled to unite with Invitae to form the leading hub for precision oncology, diagnostics, therapy optimization and monitoring, with an opportunity to accelerate both patient care and shareholder value," said Jason Myers, Ph.D., chief executive officer and co-founder of ArcherDX. "ArcherDX was founded to democratize precision oncology with best-in-class products that are personal, actionable and available in local care settings. We see STRATAFIDE DX as a significant near-term value driver, currently under development for cancer therapy optimization, while PCM provides an exciting opportunity to transform cancer care through multiple monitoring applications. ArcherDX products, workflow and powerful bioinformatics solutions provide an opportunity to advance precision oncology into regional and community settings and address an estimated $45 billion market opportunity. Together with Invitae, we look forward to expanding our impact beyond oncology, driving significant value through shared expertise to inform healthcare throughout life, globally."

"Integrating all aspects of cancer genetics can transform care for patients and the flexibility that comes from both centralized and decentralized capabilities will uniquely position Invitae to meet the needs of customers worldwide," continued Dr. George. "By joining together, we will unite world-class capabilities in the hands of a talented team with complementary expertise and strong brands in service of a shared goal to improve healthcare for patients."

Accelerating access and adoption of genetics to improve cancer care

Broad adoption of precision oncology has been limited, particularly in regional and community settings where approximately 85 percent of patients receive care.1 Without precision oncology, late-stage cancer patients can suffer from poor prognosis and outcomes, while early-stage patients may receive an inaccurate prognosis that results in unnecessary treatment and delayed detection of recurrence.2,3

Uniting Invitae and ArcherDX will offer comprehensive support for precision oncology.

Invitae has quickly become a leader in diagnostic and hereditary risk testing and has strong relationships with clinicians caring for cancer patients, including cancer genetic counselors, oncologists and imaging centers.
ArcherDX’s platform, with its proprietary Anchored Multiplex PCR (AMP) chemistry at the core, has enabled it to develop industry-leading products and services under investigation to optimize therapy and enable cancer monitoring across liquid and tissue samples.
ArcherDX has developed and commercialized over 325 unique products, including research products and services in use by more than 300 laboratories worldwide and has collaborated with more than 50 biopharmaceutical companies and contract research organizations (CROs), providing services that enable biopharmaceutical companies, including partners such as AstraZeneca, BMS and Bayer, to cost-effectively accelerate drug development.
ArcherDX is also currently developing in-vitro diagnostic (IVD) products, including STRATAFIDE DX, for therapy optimization, an estimated $5 billion market opportunity with U.S. Food and Drug Administration (FDA) submissions planned this year, and the broadly applicable Personalized Cancer Monitoring (PCM) in development for disease recurrence monitoring, therapy optimization including selection, response and modulation. Both STRATAFIDE DX and PCM have received Breakthrough Device designation from the FDA.
Together, the company will be ideally positioned to serve customers across the continuum, from individuals and community clinicians to biopharmaceutical partners, distribution partners, reference laboratories and academic centers. Invitae’s central laboratory provides support for customers who prefer to send out and can benefit from a full suite of services including reporting, clinician consultation and genetic counseling for patients, while ArcherDX’s decentralized model supports geographies and customers where local control of patient reporting is either desired or required.
With both centralized and local testing capabilities, the combined organization will offer breadth and flexibility in serving customers in more than 95 markets. Together, Invitae and ArcherDX will offer robust support for biopharmaceutical companies, from patient identification and screening, to biomarker identification and companion diagnostic development.

Transaction Terms

Under the terms of the agreement, Invitae will acquire ArcherDX for upfront consideration consisting of 30 million shares of Invitae common stock and $325 million in cash, plus up to an additional 27 million shares of Invitae common stock payable in connection with the achievement of certain milestones, for an overall transaction valued at approximately $1.4 billion. The transaction, which has been unanimously approved by the Boards of Directors of both companies, is expected to close in several months, subject to customary closing conditions including approval by the stockholders of Invitae and ArcherDX.

Financing Activities

In connection with the proposed combination, Invitae has arranged a strategic financing with over $400 million in financing commitments from a premier syndicate of life sciences investors, led by Perceptive Advisors. Invitae has entered into a definitive agreement to sell $275 million in common stock in a private placement at a price of $16.85 per share. The private placement is being supported by key existing investors in Invitae and Archer, including Casdin Capital, Deerfield Management, Driehaus Capital Management, Farallon, PBM Capital, Perceptive Advisors, Redmile Group, Rock Springs Capital, Soleus Capital, and one additional institutional investor. The placement is expected to close concurrently with the proposed combination, subject to the satisfaction of customary closing conditions. Invitae has also entered into a fully committed credit facility for up to $200 million with Perceptive Credit Opportunities Funds, subject to certain customary closing conditions.

Since the filing of its Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, Invitae has sold under its ATM facility approximately 2.6 million shares of common stock for aggregate gross proceeds of $46 million at an average price of $17.59 per share.

Invitae’s current expectations regarding its cash at transaction close would be approximately $425 million and its annualized near-term forward cash burn is expected to be approximately $130 million.

Advisors

Perella Weinberg Partners served as lead financial advisor to Invitae in connection with the business combination and Cowen served as co-financial advisor. Cowen served as lead-placement agent to Invitae for the private placement and Perella Weinberg Partners served as co-placement agent; Cowen served as exclusive financial advisor to Invitae in connection with the senior secured term loan facility. Evercore and J.P. Morgan Securities LLC acted as financial advisors to Archer.

Webcast

Management will host a conference call and webcast today at 5:00 a.m. PT / 6:00 a.m. MT / 8:00 a.m. ET to discuss the transaction. The dial-in numbers for the conference call are (866) 324-3683 for domestic callers and (509) 844-0959 for international callers, and the reservation number for both is 7097864. Please note, after dialing in, you will be prompted to enter the Conference ID and then the pound "#" sign to enter the call. Following prepared remarks, management will respond to questions from analysts, subject to time limitations.

The live webcast of the call and slide deck may be accessed by visiting the investors section of the company’s website at ir.invitae.com. A replay of the webcast and conference call will be available shortly after the conclusion of the call and will be archived on the company’s website.

On June 22, 2020 Ascentage Pharma (6855.HK), a global, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and senescence diseases, reported a clinical collaboration with Acerta Pharma, the hematology research and development center of excellence of AstraZeneca (LSE/STO/NYSE: AZN) (Press release, Ascentage Pharma, JUN 22, 2020, View Source [SID1234561370]). Under the terms of the collaboration, Ascentage will sponsor a clinical trial to study the combination of Ascentage Pharma’s APG-2575, a selective Bcl-2 inhibitor, and Acerta’s CALQUENCE (acalabrutinib), a Bruton’s Tyrosine Kinase (BTK) inhibitor, evaluating the efficacy and safety of this combination therapy in patients with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

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This global, multicenter, open-label Phase Ib/II dose-escalation and dose-expansion study is designed to evaluate the safety, tolerability, and anticancer activity of APG-2575 as a single agent or in combination with CALQUENCE in patients with r/r CLL/SLL. The study has already initiated in US with the dosing of first patient, and planned to expand in Europe, and Australia.

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms and constitutes the most common form of adult leukemia in North America and Europe, accounting for about 30% of all new leukemia cases. Despite significant initial responses to current first-line treatments, many patients with CLL need ongoing treatment to maintain these responses, and relapse often portends a poor prognosis. Recent studies in CLL showed that combining a BTK inhibitor with another Bcl-2 inhibitor can deepen responses and even shorten cyclic treatment, enabling patients to achieve complete remission and therefore discontinue treatment.1,2 These findings have provided a compelling rationale for exploring APG-2575 in combination with BTK inhibitors.

"We are delighted to enter this collaboration with Acerta. APG-2575 is a key drug candidate in our development pipeline targeting apoptosis, with great potential in the treatment of hematologic malignancies. Collaborating with Acerta helps to accelerate our global clinical development program for APG-2575," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "Combination therapy is becoming more important in cancer treatment, and the rationale of a Bcl-2 inhibitor combined with a BTK inhibitor is sound. We hope that APG-2575 combined with CALQUENCE will show synergistic effects in the treatment of CLL/SLL, offering additional treatment options for patients with otherwise limited treatment options around the world."

References

1. Jain N, Keating M, Thompson P, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med 2019;380:2095-2103.
2. Wiestner A. Ibrutinib and venetoclax — doubling down on CLL. N Engl J Med 2019;380:2169-2171.

About APG-2575

APG-2575 is a novel, orally administered Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat a variety of hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. Since March 2020, the company has received approvals and clearances for several Phase Ib/II studies of APG-2575 in China, Australia, and the US, and is advancing clinical development of APG-2575 for a variety of hematologic malignancy indications.

On June 22, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported the presentation of new preclinical data for its folate receptor alpha (FolRα) targeting antibody-drug conjugate, STRO-002, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22-24, 2020 (Press release, Sutro Biopharma, JUN 22, 2020, View Source;301080795.html [SID1234561369]). The data, being presented by Sutro’s Chief Scientific Officer, Trevor Hallam, Ph.D., demonstrates STRO-002’s immune-modulating properties and potentiation by PD-L1 blockade.

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The results of the study showed that in FolRα positive tumor cells, STRO-002 treatment induced hallmarks of immunogenic cell death, killing tumor cells while activating immune cells, including monocytes. When combined in mouse tumor models with avelumab, an anti-human & mouse PD-L1 monoclonal antibody, the combination treatment enhanced efficacy leading to more complete responses and increased killer T cells, than either agent alone. Importantly, the data suggest that a single dose of STRO-002 when combined with a PD-1/PD-L1 blockade could provide an effective and protective anti-tumor immune response.

"These data suggest that STRO-002 can drive immune-modulatory responses that can cause complete tumor regression, tumor specific T cell activation and adaptive anti-tumor immunity," said Dr. Hallam. "The results here support the clinical evaluation of STRO-002 in combination with anti-PD1 or anti-PD-L1 agents. While we believe STRO-002 as a single agent may demonstrate clinical benefit in certain tumors resistant to checkpoint inhibitor monotherapies, we are excited at the prospect of evaluating potential additional positive impacts on cancer patients that may result from combination treatment regimens involving STRO-002 with other checkpoint inhibitors."

"An important part of our STRO-002 clinical development strategy includes evaluating these data to determine an optimal combination regimen to take into clinical trials," said Sutro Chief Medical Officer, Arturo Molina, M.D. "We anticipate evaluating STRO-002 in combination studies in addition to our single agent studies. We currently expect to initiate a STRO-002 combination clinical trial in 2021."

STRO-002 is an antibody-drug conjugate directed against FolRα, a membrane receptor glycoprotein, which is highly expressed in ovarian cancer and endometrial cancer and is composed of a FolRα antibody conjugated to a tubulin inhibitor hemiasterlin using a cleavable linker.

A Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is ongoing, designed to identify the maximum tolerated dose, the recommended Phase 2 clinical dose, and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. The trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

Presentation Details:

Title: STRO-002, an anti-FolRα ADC, demonstrates immune-modulating properties
and potentiates PD-L1 blockade
Abstract Number: 2250
Session Title: Immune Mechanisms Invoked by Therapies 2
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Trevor Hallam, Ph.D.

The e-poster presentation can be found on the AACR (Free AACR Whitepaper) website and is also accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of Sutro Biopharma’s website at www.sutrobio.com on the day of the poster presentation.

Additionally, on June 24th Sutro’s partner Merck KGaA, Darmstadt, Germany, will be presenting preclinical data from the collaboration’s pre-Development Candidate, M1231, a first-in-class bispecific antibody-drug conjugate targeting EGFR and MUC1.

Presentation Details:

Title: M1231: A first-in-class bispecific antibody-drug conjugate targeting EGFR
and MUC1
Abstract Number: 5686
Session Title: Emerging Mechanisms of Resistance to Targeted Therapies
Date/Time: June 24, 2020, 10:05 a.m. – 10:15 a.m. EDT
Presenter: Jan Anderl, Ph.D.

On June 22, 2020 Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported that preclinical data of dual LSD1 and HDAC6 inhibitor JBI-802, will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II (Press release, Jubilant Therapeutics, JUN 22, 2020, View Source [SID1234561368]). The preclinical data demonstrated that JBI-802 has strong efficacy in multiple in vivo cancer models mediated by LSD1 and HDAC6 inhibition, while demonstrating excellent selectivity against other HDACs and superior in vivo efficacy compared to single agents targeting LSD1 or HDAC6.

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"We are excited to reveal these new data from our study of JBI-802 whose first-in-class dual mechanism of action targets the overexpression of two proteins, while exhibiting a favorable tolerability profile," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics Inc. "These data support the additional development of this novel dual epigenetic inhibitor as a potential therapeutic agent for genetically-defined cancers."

A link to the e-poster, listed below, is available through the AACR (Free AACR Whitepaper) website.

Title: Novel Dual Small Molecule Inhibitor Targeting LSD1 and HDAC6
Poster Number: 1756
Date and Time: June 22, 2020 at 8:45 a.m. Eastern Daylight Time (EDT)
Session Title: Epigenetic Targets
Presenter: Dhanalakshmi Sivanandhan, et al.

Key highlights from the study which examined anti-proliferative activity of JBI-802 on select acute myeloid leukemia (AML), chronic lymphocytic leukemia, small cell lung cancer, sarcoma and multiple myeloma cell lines as compared to single agents, include the following:

JBI-802 demonstrated strong tumor growth inhibition in erythroleukemia and multiple other hematological tumors as compared to single agents;
Syngeneic models showed single agent activity with unique mechanism of action and that JBI-802 can be combined with checkpoint inhibitors safely in this mouse model; and
The molecule showed a favorable tolerability profile at efficacious doses.
JBI-802 is currently being evaluated in IND-enabling studies for the treatment of AML and other solid tumors and first-in-human clinical studies are expected in 1H 2021. Jubilant Therapeutics Inc. is developing a pipeline of novel, differentiated therapeutic assets; for partnership opportunity inquiries please contact [email protected].