On February 21, 2019 Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Immune Design (NASDAQ: IMDZ), reported that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire Immune Design for $5.85 per share in cash for an approximate value of $300 million (Press release, Merck & Co, FEB 21, 2019, View Source [SID1234533525]).

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"Scientists at Immune Design have established a unique portfolio of approaches to cancer immunization and adjuvant systems designed to enhance the ability of a vaccine to protect against infection, which could meaningfully improve vaccine development," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "This acquisition builds upon Merck’s industry-leading programs that harness the power of the immune system to prevent and treat disease."

Immune Design is a late-stage immunotherapy company employing next-generation in vivo approaches to enable the body’s immune system to fight disease. The company’s proprietary technologies, GLAAS and ZVex, are engineered to activate the immune system’s natural ability to generate and/or expand antigen-specific cytotoxic immune cells to fight cancer and other chronic diseases.

"Merck has a rich history of discovery and innovation and a strong track record of developing meaningful therapeutics and vaccines," said Dr. Carlos Paya, president and chief executive officer, Immune Design. "We believe this agreement creates shareholder value by positioning our technologies and capabilities for long-term success with a leading, research-driven biopharmaceutical company."

Under the terms of the acquisition agreement announced today, Merck, through a subsidiary, will initiate a tender offer to acquire all outstanding shares of Immune Design. The closing of the tender offer will be subject to certain conditions, including the tender of shares representing at least a majority of the total number of Immune Design’s outstanding shares, the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. Upon the successful completion of the tender offer, Merck will acquire all shares not acquired in the tender through a second-step merger. The transaction is expected to close early in the second quarter of 2019.

Credit Suisse acted as financial advisor to Merck in this transaction and Gibson, Dunn & Crutcher LLP as its legal advisor. Lazard acted as financial advisor to Immune Design and Cooley LLP as its legal advisor.

Important Information about the Tender Offer

The tender offer described in this press release (the "Offer") has not yet commenced. This press release is for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell any shares of the common stock of Immune Design ("IMDZ") or any other securities. At the time the planned tender offer is commenced, a tender offer statement on Schedule TO, including an offer to purchase, a letter of transmittal and related documents, will be filed by Merck Sharp & Dohme Corp. ("Merck") and Cascade Merger Sub Inc., a wholly-owned subsidiary of Merck ("Buyer"), with the Securities and Exchange Commission (the "SEC"), and a solicitation/recommendation statement on Schedule 14D-9 will be filed by Immune Design with the SEC. The offer to purchase shares of Immune Design common stock will only be made pursuant to the offer to purchase, the letter of transmittal and related documents filed as a part of the Schedule TO.

INVESTORS AND SECURITY HOLDERS ARE URGED TO READ BOTH THE TENDER OFFER STATEMENT AND THE SOLICITATION/RECOMMENDATION STATEMENT REGARDING THE OFFER, AS THEY MAY BE AMENDED FROM TIME TO TIME, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION.

Investors and security holders may obtain a free copy of these statements (when available) and other documents filed with the SEC at the website maintained by the SEC at www.sec.gov or by directing such requests to the Information Agent for the Offer, which will be named in the tender offer statement. Additional copies of the tender offer materials may be obtained at no charge by contacting Merck at 2000 Galloping Hill Road, Kenilworth, N.J., 07033 or by phoning (908) 423-1000. In addition, Merck and Immune Design file annual, quarterly and current reports and other information with the SEC. You may read and copy any reports or other information filed by Merck or Immune Design at the SEC public reference room at 100 F Street, N.E., Washington, D.C., 20549. For further information on the SEC public reference room, please call 1-800-SEC-0330. Merck’s and Immune Design’s filings with the SEC are also available to the public from commercial document-retrieval services and at the SEC’s website at www.sec.gov.

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On February 20, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-402 (loncastuximab tesirine) in combination with Pharmacyclics LLC’s ibrutinib in patients with advanced diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) (Press release, ADC Therapeutics, FEB 20, 2019, View Source [SID1234596064]).

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ADCT-402, an ADC designed to target and kill CD19-expressing malignant B-cells, is also being evaluated in an ongoing pivotal Phase II clinical trial in patients with relapsed or refractory (R/R) DLBCL and a Phase I clinical trial in combination with IMFINZI (durvalumab) in patients with multiple types of R/R non-Hodgkin lymphoma. Ibrutinib, a small-molecule inhibitor of Bruton’s tyrosine kinase that is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc., is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. Ibrutinib is approved for use in patients with R/R MCL and has shown some activity in R/R DLBCL.

Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, "At the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the data we presented from our 183-patient first-in-human clinical trial of ADCT-402 demonstrated its encouraging safety profile and anti-tumor activity as a single agent against relapsed or refractory diffuse large B-cell lymphoma and mantle cell lymphoma. Now, in our second combination trial of ADCT-402, we look forward to exploring whether ADCT-402 and ibrutinib, both of which target B-cell cancers with different mechanisms of action, may increase the response rate and durability of response compared to the effects of these compounds as single agents."

Julien Depaus, MD, an investigator for the trial at CHU UCL Namur, Yvoir, Belgium, said, "Unfortunately, a significant number of patients with B-cell malignancies will relapse after initial treatment. As the prognosis for these patients is poor, it is important to evaluate potential viable new treatments for relapsed or refractory diffuse large B-cell lymphoma and mantle cell lymphoma, such as the combination of ADCT-402 and ibrutinib we are studying in this Phase I trial."

The open-label, single-arm trial will include a dose-escalation part, followed by a dose-expansion part. The dose-expansion part may have up to two cohorts, one for DLBCL and one for MCL, in order to obtain additional safety and preliminary anti-tumor activity information at the maximum tolerated dose. Approximately 60 patients will be enrolled in the trial. For more information, please visit www.clinicaltrials.gov (identifier NCT03684694).

ADCT-402 Interim First-in-Human Data

Updated data from the ongoing 183-patient Phase I clinical trial of ADCT-402 were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In a subpopulation of 139 evaluable patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had failed or were intolerant to established therapies, ADCT-402 demonstrated manageable toxicity. At doses >120 μg/kg, the overall response rate (ORR) was 43.3 percent (55/127 patients with DLBCL), comprising 23.6 percent complete responses and 19.7 percent partial responses. In a subgroup of 15 patients with mantle cell lymphoma (MCL), ADCT-402 demonstrated manageable toxicity, and ORR was 46.7 percent (7/15) and median duration of response was not reached after a median follow-up time of 8.7 months.

About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (NCT03589469), a Phase I clinical trial in combination with IMFINZI (durvalumab) in patients with R/R DLBCL, mantle cell lymphoma or follicular lymphoma (NCT03685344) and a Phase I clinical trial in combination with ibrutinib in patients with R/R DLBCL or mantle cell lymphoma (NCT03684694). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and MCL.

On February 20, 2019 Sunstar, a multi-national healthcare company based on oral care reported the acquisition from BMG Pharma S.p.A. of the innovative cancer supportive care product, GelX (Press release, SUNSTAR Americas, FEB 20, 2019, View Source [SID1234553908]). Through this acquisition Sunstar gains global distribution of this product line, expanding its position as a global leader in the development and commercialisation of oral healthcare products, mainly marketed under the GUM brand.

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BMG Pharma S.p.A, an innovative specialty pharmaceutical company, will invest the proceeds from this transaction into the rapid development completion of a number of new patent protected products with topical, subcutaneous dermatology, osteoarthritis and oral care applications, which it will be able to offer to its network of global marketing partners.

Takeshi Kamigouchi, CEO of Sunstar Suisse SA, commented– "We are proud and excited to distribute the superior product GelX to make the difference in cancer patients’ oral conditions globally. Our purpose is to develop and provide products and services that promote mouth & body concept to extend people’s healthy lifespan and improve their quality of life. GelX is truly expected as a product that plays a key role that demonstrates we are the purpose driven company."

Marco Mastrodonato, CEO of BMG Pharma S.p.A., commented– "I have been partnering with Sunstar since 2002 with a win-win partnership in the oral care segment and at BMG are very proud to be the development and provider partner to a global oral care market leader. This is an important step for the company, bringing a strategic investment which represents a significant growth opportunity by allowing focus on the rapid completion of a number of products in our pipeline with unique propositions.

On February 20, 2019 Torque, a clinical-stage immuno-oncology company developing first-in-class Deep Primed T Cell Therapeutics to direct immune power deep within the tumor microenvironment, reported that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside of the U.S. and Canada) (Press release, Torque Therapeutics, FEB 20, 2019, View Source [SID1234553880]). The collaboration will evaluate Torque’s Deep IL-15 Primed T Cells (TRQ-1501) both as a single agent and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in a Phase 1/2 study in multiple solid tumor indications.

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"We are very excited about this clinical collaboration with Merck to evaluate the combination of KEYTRUDA with our Deep IL-15 Primed T cells," said Bart Henderson, Chief Executive Officer of Torque. "Torque’s new class of cellular immunotherapy is designed to harness the full biology of natural T cells for treating multiple solid tumors, and we believe the combination with anti-PD-1 therapy will further enhance the function of these cells by protecting them against immunosuppression in the tumor microenvironment. This combination has the potential to improve treatment outcomes for patients with solid tumors that are relapsed or refractory to currently available treatments and broaden the applications of cellular immunotherapy."

The Phase 1/2 trial will evaluate the safety, tolerability, immune biomarkers, and overall response rates achieved with TRQ-1501 in combination with KEYTRUDA in two groups of patients:

Patients with melanoma, non-small cell lung cancer, bladder cancer, renal cell carcinoma, and head and neck cancer who are relapsed or refractory to checkpoint inhibitor therapy (anti PD-1/PD-L1 inhibitor treatment)
Patients with advanced or metastatic ovarian cancer or sarcoma who are relapsed or refractory to standard-of-care treatments
Torque will conduct the trial at multiple clinical sites in the U.S. and expects to commence the combination arm of the study with KEYTRUDA later this year.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.

About TRQ-1501
Torque is developing a new class of Deep-Primed cellular immunotherapy designed to overcome the key challenges limiting broad use of cellular therapy in oncology, including the capability to target tumors that express multiple heterogeneous antigens, the ability to overcome the immunosuppressive microenvironment that shuts down T cell function, and the need for outpatient treatment with a high margin of safety. Torque uses its Deep-Priming technology to develop multi-targeted, antigen-primed T cells that carry surface-anchored immune-stimulatory drugs to drive a full immune response within the tumor microenvironment against tumors with heterogenous antigens. TRQ-1501 is an investigational immune cell therapy produced from a patient’s own T cells, which are primed to be active against multiple tumor-associated antigens and loaded with Deep IL-15 (a multimer of IL-15 cytokine) anchored to the T cells’ surface.

About Torque’s Deep-Primed Immune Cell Therapy Platform
Torque’s Deep-Priming platform uses advanced cell process engineering to:

prime and activate T cells to target multiple tumor antigens and
tether immune-stimulatory drugs to the surface of these multi-target T cells to direct immune activation in the tumor microenvironment
using a proprietary technology platform, without genetic engineering, for a high margin of safety.
Deep-Primed T cells both target multiple tumor antigens and pharmacologically activate an immune response with anchored cytokines. This process does not require genetic engineering of the T cells and so preserves the natural T cell receptor for delivering a regulated immune response, with the potential for a high margin of safety. In addition to antigen priming, immunomodulators are tethered to the surface of Deep-Primed T cells—initially IL-15 and IL-12 cytokines, and TLR agonists—that activate both innate and adaptive immunity. Administering these immunomodulators systemically to a patient can cause lethal toxicity by activating immune cells throughout the body. By loading precise doses of cytokines onto the surface of T cells, Deep Priming focuses the immune response to target the tumor, without systemic exposure.

In hematologic cancers, this new class of immune cell therapeutics has the potential to improve on the initial success of single-target CAR T therapeutics with expanded efficacy and also move cell therapy treatment out of the hospital with a high margin of safety. For solid tumors, Deep-Primed T cells have the potential to enable efficacy against tumors with heterogeneous antigens protected by hostile microenvironments, which are not readily addressable with the first generation of immune cell therapies.