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Lantheus and Progenics Agree to Amended Transaction Terms

On February 20, 2020 Lantheus Holdings, Inc. (NASDAQ: LNTH) ("Lantheus"), parent company of Lantheus Medical Imaging, Inc. ("LMI"), a leader in the development, manufacture and commercialization of innovative diagnostic imaging agents and products, and Progenics Pharmaceuticals, Inc. (NASDAQ: PGNX) ("Progenics"), an oncology company developing innovative medicines and artificial intelligence to find, fight and follow cancer, reported that they have entered into an Amended and Restated Agreement and Plan of Merger (the "Amended Agreement") which amends the previously announced definitive Agreement and Plan of Merger dated as of October 1, 2019 (the "Original Agreement") (Press release, Progenics Pharmaceuticals, FEB 20, 2020, View Source [SID1234554556]). The Amended Agreement has been unanimously approved by the Boards of Directors of both companies.

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Under the terms of the Amended Agreement, Lantheus will acquire all of the issued and outstanding shares of Progenics common stock at a fixed exchange ratio whereby Progenics stockholders will receive, for each share of Progenics stock held at the time of the closing of the merger, 0.31 of a share of Lantheus common stock, increased from 0.2502 under the Original Agreement, together with a non-tradeable contingent value right ("CVR"). The CVR is payable in two separate cash payments if PyLTM (18F-DCFPyL), Progenics’ prostate-specific membrane antigen targeted imaging agent designed to visualize prostate cancer currently in late stage clinical development ("PyL"), exceeds net sales thresholds of $100 million in 2022 and $150 million in 2023. As a result of the increase in the exchange ratio, following the completion of the merger, former Progenics stockholders’ aggregate ownership stake will increase to approximately 40% of the combined company from approximately 35% under the terms set forth in the Original Agreement.

Mary Anne Heino, President and Chief Executive Officer of Lantheus, said, "After continued integration planning with Progenics and close collaboration with Progenics’ reconstituted Board of Directors, we are even more excited about the potential value we can unlock by combining our two businesses. We remain confident that together, we will create a platform that leverages Lantheus’ long-standing expertise in complex manufacturing, supply chain and commercial excellence, with Progenics’ three leading FDA approved products, clinical pipeline and development capabilities. Our team enthusiastically shares the view of Progenics stockholders in the long-term growth potential of the Progenics product portfolio and, with our complementary strengths, our combined company will be better able to serve patients and healthcare professionals across the continuum of critical diagnosis and care. We are also pleased with the progress the two companies have made toward closing throughout our discussions."

Gérard Ber, Ph.D. and Mr. Heinz Mäusli, two members of Progenics’ reconstituted Board, will join the Lantheus Board upon closing. Lantheus will reduce its current ten member Board to nine members at its 2020 stockholders meeting, or sooner if this transaction closes before then. Lantheus will further reduce its Board to eight members at its 2021 stockholders meeting. As previously announced, the combined company will be led by Lantheus Chief Executive Officer Mary Anne Heino, who will be supported by Chief Financial Officer Robert J. Marshall Jr., CFA, and Chief Operations Officer John Bolla.

Brian Markison, Chairman of the Board of Lantheus, said, "We are excited about the additions of Dr. Ber and Mr. Mäusli to our board. Both Dr. Ber and Mr. Mäusli add experience in radiopharmaceuticals with deep manufacturing, operating, finance and compliance experience."

Ann MacDougall, Interim Chair of Progenics’ Board, said, "We have been pleased to work with Lantheus on the amended merger agreement. The Progenics’ Board has unanimously determined that the combination with Lantheus under the updated terms is in the best interest of our stockholders. The merger creates a stronger combined platform that offers an innovative and diversified diagnostic and therapeutics portfolio while ensuring stockholders the opportunity to participate in the future potential upside through enhanced ownership and the CVRs. The reconstituted Progenics Board, assisted by independent financial and legal advisors, has evaluated the business prospects and operations of Progenics as a stand-alone business as well as the value of the Progenics interest in the combined company under the revised terms in the merger transaction, and have concluded that the combination is the better path forward. We are also pleased to have our directors, Dr. Gérard Ber and Mr. Heinz Mäusli, join the Board of the combined company to enhance its prospects for future success."

David Mims, Interim CEO of Progenics, added, "We believe the combination will add significant value to both companies’ stockholders, especially in light of the recent positive results we achieved with our PyL Phase 3 CONDOR trial and our product pipeline and research and development capabilities."

Lantheus’ Strategic Plan for Progenics

As previously announced on November 7, 2019, Lantheus provided a strategic plan that provides stockholders of both companies with a clear and thoughtful strategy in which Lantheus will leverage its existing infrastructure and long-standing expertise to deliver on the promise of Progenics’ product portfolio and maximize value for all stockholders. The Lantheus team remains confident in the combination with Progenics as Lantheus has a clear track record of creating significant stockholder value, built on in-house operational excellence, commercial expertise, financial discipline and robust corporate governance.

In addition, through its extensive due diligence process and continued discussions with the Progenics Board, Lantheus has identified actions and investments in 2020 that will help enhance the progress of AZEDRA and the PyL and 1095 programs. Lantheus remains well-positioned to ensure that the Progenics portfolio has the benefit of access to cost-effective capital, manufacturing capabilities, logistical support and personnel resources to succeed.

With a focus on commercial, operational and clinical enhancements under the management of its proven team, Lantheus’ strategic plan represents the highest value, most certain and expedient path forward to drive significant, long-term value for stockholders of both Progenics and Lantheus.

Strong Financial Rationale

As a result of the recently reported positive top line results from the PyL Phase 3 CONDOR trial and ongoing integration planning, Lantheus believes this combination can generate double digit revenue growth, as well as drive margin expansion through the previously disclosed 2023 planning horizon. Accordingly, Lantheus continues to believe it can achieve adjusted EPS accretion in the third year following the close of the transaction.

Additional Transaction Details

Lantheus has also agreed to make available to Progenics up to $10 million of bridge financing on terms mutually agreed upon by the parties. The merger transaction is expected to close early in the second quarter of 2020, subject to approval by Lantheus and Progenics stockholders and satisfaction of other customary closing conditions.

Upon completion of the acquisition, the combined company will continue to be headquartered in North Billerica, Massachusetts and will trade on the NASDAQ under the ticker symbol: LNTH.

Advisors

SVB Leerink LLC is acting as financial advisor and White & Case LLP is acting as legal counsel to Lantheus. Progenics engaged BofA Securities, Inc. as financial advisor and previously engaged Jefferies LLC as existing lead financial advisor. Covington & Burling LLP and Mayer Brown LLP serve as independent legal advisors to Progenics.

Lantheus’ comprehensive strategic plan, along with additional documents related to its proposed acquisition of Progenics, can be viewed at www.lantheusprogenics.transactionannouncement.com/, and can also be viewed on the SEC’s website at www.sec.gov.

AbbVie Declares Quarterly Dividend

On February 20, 2020 The board of directors of AbbVie Inc. (NYSE: ABBV) reported a quarterly cash dividend of $1.18 per share (Press release, AbbVie, FEB 20, 2020, View Source [SID1234554555]).

The cash dividend is payable May 15, 2020 to stockholders of record at the close of business on April 15, 2020.

Since the company’s inception in 2013, AbbVie has increased its dividend by 195 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.

Study shows long-term survival benefit for certain patients with advanced lung cancer

On February 20, 2020 Yale Cancer Center researchers, reported that even a tiny amount of a biomarker known as PD-L1 (programmed death-ligand1) can predict a long-term survival benefit from using pembrolizumab (Keytruda) (Press release, Yale University, FEB 20, 2020, View Source [SID1234554554]). The drug is one of the first checkpoint inhibitors to be developed and used in cancer treatment. The findings are published online today in the Journal of Clinical Oncology.

"The response that we have seen from pembrolizumab, in a subset of patients years after treatment ended, is remarkable, especially since their chemotherapy had initially failed," said Roy S. Herbst, M.D., Ph.D., chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital and Associate Cancer Center Director for Translational Research at Yale Cancer Center.

The findings come from the phase III KEYNOTE-010 clinical trial, which was conducted in 202 academic medical centers in 24 countries. The study enrolled patients who had previously been treated unsuccessfully with chemotherapy for stage 3 or 4 non-small cell lung cancer (NSCLC), the most common type of lung cancer. The study compared use of pembrolizumab in 690 patients to treatment of docetaxel chemotherapy in 343 patients. In the 79 of 690 patients who received two years of pembrolizumab, overall survival was about 99% one year after discontinuing treatment. Overall, survival in this group three years after the two-year treatment period ranged from 23% to 35%, depending on how much of the PD-L1 biomarker their cancer expressed, compared with 11% to 13% in patients receiving chemotherapy.

Even more surprising, Herbst added, is that some patients whose cancer recurred after an initial two years of treatment responded to pembrolizumab when the drug was offered again.

"Before we had pembrolizumab, survival from advanced lung cancer was measured in months, not years," Herbst said. "It is too soon to say that pembrolizumab is a potential cure for a substantial number of patients whose tumors express PD-L1, and we know that it doesn’t work for all patients, but, the agent remains very, very promising. The majority of patients who completed two years of treatment remain in remission and those who had recurrence could be retreated with pembrolizumab at the time of progression and still achieve disease control."

The PD-L1 designation refers to the PD-1 pathway that cancer uses to hide from killer immune cells. Switching on this pathway stops these immune cells from attacking cancer cells, allowing tumors to grow and spread. Checkpoint inhibitors either block the PDL-1 protein that is expressed on the outside of tumor cells, or the PD molecule on immune cells. Pembrolizumab blocks PDL-1, freeing immune cells to target the cancer.

Investigators estimate that 75% of NSCLC patients express PD-L1 protein on their cancer cells, and within this group, up to 25% express a high amount. The rest express a lower quantity. The percentage of expression is quantified by a tumor proportion score (TPS) that "pulls" about 100 cancer cells from a tumor and counts the number of cells that express PD-L1. The amount is then described as either cancer that expresses more than 50% PD-L1 or more (TPS ?50) or 1 percent PD-L1 or more (?1).

Pembrolizumab is the first checkpoint inhibitor to test the ability of a biomarker to help determine disease control outcomes, and that biomarker has now been tested for the longest period of any clinical trial. "Currently, the agent is being used in all potential settings," Herbst added, "before any other treatment, after other treatment, and with other treatments."

"Our hope is to find the very best way to use pembrolizumab to treat individual lung cancer patients, assessing how much PD-L1 a tumor expresses, what stage the patient is in, as well as other variables and biomarkers we are working on," Herbst said. "This is the story of tailored therapy."

First Patient Dosed With Transgene’s Oncolytic Virus TG6002, Administered by Intrahepatic Artery Infusion in Colorectal Cancer With Liver Metastases

On February 20, 2020 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that the first patient has successfully received TG6002, via an intrahepatic artery (IHA) infusion, as a locoregional treatment for unresectable liver metastases from colorectal cancer (CRLM) (Press release, Transgene, FEB 20, 2020, View Source [SID1234554553]). This procedure was performed at the NHS St James’s University Hospital in Leeds (United Kingdom). Dr. Adel Samson, Academic Medical Oncologist at The Leeds Teaching Hospitals NHS Trust and The University of Leeds, is the Chief Investigator of this trial. TG6002 is a next-generation oncolytic virus which has multiple mechanisms of action, both directly in the tumor micro-environment and systemically.

The oncolytic virus TG6002 has been engineered to directly kill cancer cells (oncolysis), to enable the production of a chemotherapy agent (5-FU) within the tumor, and to elicit an immune response by the body against the tumor cells. In preclinical experiments, TG6002 has been shown to induce the shrinkage of the primary tumor as well as the regression of distant metastases1.

TG6002 has been designed to achieve a better anti-tumor effect with limited chemotherapy-induced side effects, by enabling the production of a chemotherapy agent in the tumor.

TG6002 enables the production of 5-FU by the expression of the proprietary FCU1 gene in the cancer cells TG6002 has infected, leading to local conversion of the pro-drug 5-FC (administered orally) into 5-FU.
5-FU is a common chemotherapy for patients with CRLM. However, it is associated with side effects that can lead to treatment discontinuation. With TG6002, 5-FU is produced within the tumor where it is expected to be present at a high concentration level in contrast to the very low levels anticipated in the rest of the patient’s body.
In this trial, TG6002 is administered via the intrahepatic artery (IHA).

This administration route is routinely used to deliver therapeutic agents into patients with liver tumors. The IHA route will efficiently deliver a higher concentration of TG6002 to the liver metastases (visible or not visible with CT scan).
The IHA trial is a single-arm open-label Phase 1/2a trial evaluating the safety, pharmacokinetics, biodistribution and efficacy of repeated and ascending doses of TG6002 in combination with oral 5-FC. The study will enroll up to 75 patients.
TG6002 is also being evaluated in another Phase 1/2a clinical trial where it is being given via intravenous administration in advanced GI cancer patients. The first clinical data from this trial will be reported during the second quarter of 2020.

"The start of this trial evaluating the safety and activity of TG6002 administered via an IHA infusion in patients with CRLM will enable us to further strengthen the data package for this novel oncolytic virus. IHA infusion is a novel administration mode for oncolytics and we believe it will help broaden the scope of potential indications that could be targeted by vaccinia-based oncolytics. Our on-going trial with TG6002 administered by the intravenous route is proceeding well. No safety signals have been observed so far and the dose-escalation phase is ongoing. We expect the first clinical data from this IV study to be reported during the second quarter of 2020." said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

Dr. Samson added: "Previous trials with vaccinia-based oncolytic viruses have shown that these novel immunotherapeutics can modulate the tumor micro-environment. The addition of the local production of chemotherapy offers new perspectives in the treatment of CRLM patients. The use of IHA infusion should enable a higher concentration of TG6002 in the liver tumors allowing it to become an additional effective and well tolerated treatment modality. I hope that this study will demonstrate that the multiple mechanisms of action of TG6002 are able to achieve better outcomes for the patients whilst limiting systemic exposure to 5-FU."

This work was supported by Yorkshire Cancer Research and the National Institute for Health Research Leeds Clinical Research Facility.

About TG6002
TG6002 is a next generation oncolytic immunotherapy. It has been designed to induce the breakdown of cancer cells (oncolysis) and allow the local production of chemotherapy (5-FU) in the tumor. TG6002 is a modified Vaccinia virus, with double gene deletion (TK-RR-), and expressing the proprietary FCU1 gene in the cancer cells it has infected, leading to the local conversion of the non-cytotoxic pro-drug, flucytosine (5-FC), into 5-FU, a widely used cancer chemotherapy. The oncolytic virus TG6002 has shown efficacy and good safety profile in several preclinical models. Transgene believes that TG6002 may represent a new therapeutic option in recurrent cancer patients.

About Colorectal cancer
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide. In 2018, there were approximately 500,000 new cases of CRC in Europe with 242,000 deaths and worldwide, there were 1.8 million new cases with 881,000 deaths (Globocan 2018). Approximately half of all CRC patients develop liver metastases, only a small proportion of whom being suitable for potentially curative hepatic resection (Leporrier J, 2006). Over the last decade, the clinical outcome for patients with metastatic CRC (mCRC) has improved. Today, the median overall survival (OS) for patients with mCRC is ∼30 months.

Agenus Announces Positive Interim Data from Balstilimab and Zalifrelimab Clinical Trials in Second-Line Cervical Cancer

On February 20, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents designed to activate immune response to cancers, reported new clinical data from pre-planned interim analyses of balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4) and data from a dose escalation study of AGEN1181, a novel multi-functional enhanced CTLA-4 antibody (Press release, Agenus, FEB 20, 2020, View Source [SID1234554552]).

The interim analysis from 34 evaluable patients treated with the combination of balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4) demonstrated a 20.6% overall response rate (ORR), which included a complete response (CR) rate of 8.8% in second-line cervical cancer. The interim analysis from 44 evaluable patients treated with balstilimab monotherapy demonstrated an ORR of 11.4% in second-line cervical cancer. The clinical activity observed in both studies are comparable to other agents in these therapeutic classes. Both balstilimab monotherapy and the combination of balstilimab and zalifrelimab were well-tolerated with no new safety signals.

Additionally, early clinical data from a dose-escalation study of AGEN1181 revealed a confirmed CR in a patient with a difficult-to-treat, PD-L1 negative, microsatellite stable, endometrial cancer. The patient was treated with a low dose of AGEN1181 (1 mg/kg) and had failed prior treatment with a PD-1 inhibitor. Additionally, stable disease was noted in the majority of patients treated. AGEN1181 monotherapy was well-tolerated. Balstilimab, zalifrelimab and AGEN1181 are investigational agents that have not been approved for any uses. Efficacy and safety have not been established.

Details for today’s Investor Day:

Date:

Thursday, February 20, 2020

Time:

9:00 – 11:00AM

Location:

New York, NY (by invitation only)

Link to Webcast

Presenters will include global experts in immune-oncology, Dr. Chuck Drake, Co-Director, Cancer Immunotherapy Program, Columbia University Herbert Irving Comprehensive Cancer Center, and Dr. Bradley Monk, M.D., FACS, FACOG, Co‐Director of GOG Partners, Arizona Oncology (US Oncology Network) and Professor, Gynecologic Oncology at University of Arizona, and Creighton University, Medical Director of US Oncology Research Gynecology program in Phoenix, Arizona.

The event will be webcast live and may be accessed by visiting the "Events & Presentations" page within the Investors section of the Agenus website at www.agenusbio.com or by using the link below. A replay of the webcast, as well as a copy of the slide presentations that will be presented at the event, will be available on the Agenus website following the event.