On April 8, 2021 Organon Finance 1 LLC, a subsidiary of Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that Organon Finance 1 LLC has priced its previously announced offering of €1,250,000,000 aggregate principal amount of 2.875% senior secured notes due 2028 (the "euro secured notes"), $2,100,000,000 aggregate principal amount of 4.125% senior secured notes due 2028 (the "U.S. dollar secured notes") and $2,000,000,000 aggregate principal amount of 5.125% senior unsecured notes due 2031 (the "unsecured notes" and together with the euro secured notes and U.S. dollar secured notes, the "notes"), in connection with the previously announced spinoff of Organon & Co. ("Organon") from Merck (Press release, Merck & Co, APR 8, 2021, View Source [SID1234577733]). As part of the spinoff, the notes will be assumed by Organon, and a Dutch private limited company and wholly owned subsidiary of Organon which will act as co-issuer of the notes.

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Organon intends to use the net proceeds from the notes offering, together with available cash on its balance sheet and borrowings under senior secured credit facilities which Organon anticipates entering into, to repay one or more intercompany loans or notes owed by Organon to a Merck affiliate and to pay fees and expenses related to the spinoff. The proceeds of the notes offering will be held in escrow until satisfaction of the conditions precedent to the spinoff and certain other escrow release conditions (the "Effective Date").

Each series of notes will be issued at an issue price of 100%. From and after the Effective Date, the euro secured notes and the U.S. dollar secured notes will be guaranteed on a senior secured basis, and the unsecured notes will be guaranteed on a senior unsecured basis, jointly and severally, by all of Organon’s existing or future subsidiaries that guarantee its proposed senior secured credit facilities. Prior to the Effective Date, each series of notes will be senior secured obligations solely of the Organon Finance 1 LLC, and will not be guaranteed by Organon or any of its subsidiaries.

The notes offering is expected to close on April 22, 2021, subject to customary closing conditions.

The notes have not been and will not be registered under the U.S. Securities Act of 1933, as amended (the "Securities Act"), any state securities laws or the securities laws of any other jurisdiction, and may not be offered or sold in the United States absent registration or an applicable exemption from registration. Accordingly, the notes are being offered and sold only to persons reasonably believed to be qualified institutional buyers in accordance with Rule 144A under the Securities Act and to non-U.S. persons outside the United States in reliance on Regulation S under the Securities Act.

This announcement is an advertisement and is not a prospectus for the purposes of Regulation (EU) 2017/1129 (as amended, the "Prospectus Regulation") or Regulation (EU) 2017/1129 as it forms part of domestic law by virtue of the European Union (Withdrawal) Act 2018 (the "UK Prospectus Regulation").

In member states of the European Economic Area, this announcement is directed only at persons who are "qualified investors" within the meaning of the Prospectus Regulation. In the United Kingdom, this announcement is directed only at persons who are "qualified investors" within the meaning of the UK Prospectus Regulation.

Manufacturer target market (MiFID II product governance / UK MiFIR product governance) is eligible counterparties and professional clients only (all distribution channels). No PRIIPs key information document has been prepared as not available to retail in the EEA. No UK PRIIPs key information document has been prepared as not available to retail in the UK.

In the United Kingdom, this announcement is directed only at persons (i) that have professional experience in matters relating to investments falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "Order"); (ii) falling within Article 49(2)(a) to (d) ("high net worth companies, unincorporated associations etc.") of the Order; or (iii) at whom this announcement may otherwise be directed without contravention of Section 21 of the Financial Services and Markets Act 2000, as amended (all such persons together being referred to as "relevant persons"). This announcement must not be acted on or relied on by persons who are not relevant persons. Any investment or investment activity to which this announcement relates is available only to relevant persons and will be engaged in only with relevant persons.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any security and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful.

On April 9, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that positive initial clinical data from an investigator-sponsored study at The University of Texas MD Anderson Cancer Center evaluating cord blood-derived natural killer (cbNK) cells pre-complexed with Affimed’s innate cell engager (ICE) AFM13 (CD16A/CD30) (Press release, Affimed, APR 9, 2021, View Source [SID1234577785]).

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This approach was developed in the laboratory of Katy Rezvani, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson, who is presenting the data as part of the Major Symposia and Advances sessions at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The presentation is available for viewing by registered participants through June 21, 2021. Dr. Rezvani will take part in a live panel discussion as part of the presentation on April 13, 2021 at 1:30 p.m. EDT.

"We are encouraged by the initial safety and efficacy data from this groundbreaking first in-human study. The finding of an objective response rate of 100% amongst our first four patients enrolled is impressive," said Andreas Harstrick, M.D., Chief Medical Officer of Affimed. "These initial results indicate AFM13 may have the potential to help NK cells target and destroy cancer cells. We plan to continue to develop and customize approaches that leverage the unique and differentiating features of our ICE molecules in combination with adoptive NK cell transfer to provide options for treating a variety of hematologic and solid tumors."

The open-label, non-randomized, single-center, dose-escalation trial is evaluating the pre-complexing of AFM13 with cbNK cells followed by three weekly infusions of AFM13 monotherapy in adult patients with recurrent/refractory CD30-positive lymphomas. The trial is led by Yago Nieto, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

"There remains a high unmet need for effective treatments in relapsed/refractory (R/R) CD30+ lymphomas. We are encouraged by the data generated from the first patients treated with cbNK cells pre-complexed with AFM13," said Dr. Rezvani. "The results suggest this combination is facilitating clinical responses with minimal toxicity, warranting further study as we continue to explore novel cell therapies for our patients."

LOGO

As of March 31, 2021, three patients have been dosed with two cycles of therapy in dose cohort 1 (1×106 AFM13-cbNK/kg) and one patient has received a single cycle of therapy in dose cohort 2 (1×107 AFM13-cbNK/kg). The study is currently enrolling patients in the second dose cohort of NK cells, and further updates are expected later in 2021. Results from the first cycle of the first dose cohort are being presented by Dr. Rezvani at AACR (Free AACR Whitepaper), and Affimed is supplementing the data with best responses as of March 31, 2021, as summarized below.

Patient

number
cbNK Cell
Dose

Patient

Cancer Type

Prior Treatment

CRS/

Neurotoxicity/

GVHD

Best Response

Cohort 1 – completed
#1 1×106 / kg 43-year-old-male Hodgkin lymphoma 4 lines of therapy (ABVD, ICE, brentuximab vedotin, nivolumab + ruxolitinib) None Partial response
#2 1×106 / kg 31-year-old-male Hodgkin lymphoma 14 lines of therapy (ABVD, brentuximab vedotin, HDACi/P13Ki, pembrolizumab, nivolumab, allo-HSCT, hypercytoxan, ibrutinib, niraparib, bendamustine, everolimus) None Partial response
#3 1×106 / kg 53-year-old-female Hodgkin lymphoma 5 lines of therapy (ABVD, ICE, brentuximab vedotin, nivolumab, GemOx) None Complete response after cycle 2
Cohort 2 – ongoing (1 of 3 patients enrolled)
#4 1×107 / kg 26-year-old-male Hodgkin lymphoma 9 lines of therapy (ABVD, ICE + brentuximab vedotin, radiation, nivolumab, CD30-CART, TTI-622, brentuximab vedotin + bendamustine, allo-HSCT, brentuximab vedotin + bendamustine with brentuximab vedotin maintenance) None Complete response
ABVD = Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine (DTIC)

ICE = chemotherapy combination includes the drugs: ifosfamide, carboplatin, & etoposide phosphate

GemOx= gemcitabine, oxaliplatin

There were no observed events of cytokine release syndrome, neurotoxicity syndrome or graft-versus-host disease.

Response evaluation followed the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). All four patients had relapsed/refractory Hodgkin Lymphoma and were heavily pretreated, with between 4 and 14 previous lines of therapy which in all cases included brentuximab vedotin (Adcetris) and anti-PD1 antibodies. Of note, patient #4 had also previously received a CD30-CAR-T.

Conference Call/Webcast Details

Affimed will host a conference call and webcast on April 14, 2021, at 4:05 p.m. EDT to discuss the initial study findings. The conference call will be available via phone and webcast. To access the call, please dial +1 (646) 741-3167 for U.S. callers, or +44 (0) 2071 928338 for international callers, and reference passcode 1788338 approximately 15 minutes prior to the call.

A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be accessible at the same link for 30 days following the call.

About the Phase 1 Study

The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored Phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas. The study is a dose-escalation trial of pre-complexed NK cells, with patients receiving 1×106 NK cells/kg in Cohort 1; 1×107 NK cells/kg in Cohort 2; and, 1×108 NK cells/kg in Cohort 3. The trial is designed to explore safety and activity and determine the recommended Phase 2 dose. In each cohort, the dose of the pre-complexed NK cells with AFM13 is to be followed by weekly doses of 200 mg AFM13 monotherapy for three weeks, with each patient evaluated for dose-limiting toxicities and responses on day 28.

MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan.

Additional information about the study can be found at www.clinicaltrials.gov (NCT04074746).

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting, and additional details can be found at www.clinicaltrials.gov (NCT04101331).

On April 9, 2021 City of Hope, a world-renowned cancer research and treatment center, reported that it will showcase breakthrough research and innovative studies at the first week of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, which will take place virtually from April 10 to 15 (Press release, City of Hope, APR 9, 2021, View Source [SID1234577802]).

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City of Hope scientists will present findings that could one day lead to an effective KRAS inhibitor for solid tumors, innovative chimeric antigen receptor (CAR) T cell therapy for glioblastoma, potent CAR natural killer cell therapy against pancreatic cancer, improved health equity for marginalized communities, better ways to prevent and treat colorectal cancer, and much more.

The multidisciplinary meeting program will highlight the best cancer science and medicine in the world. Last year more than 73,000 people from 140 countries attended AACR (Free AACR Whitepaper)’s first-ever virtual meeting. Some City of Hope research that will be presented at the AACR (Free AACR Whitepaper) meeting is highlighted below.

More competition in KRAS inhibitor space: Revolution Medicine’s RMC-4630
Time: April 10 from 2:05 to 2:15 p.m. EDT
This late-breaking oral presentation led by City of Hope’s Marianna Koczywas, M.D., will address the anti-tumor activity and tolerability of the SHP2 inhibitor RMC-4630 as a single agent in patients with RAS-addicted solid cancers. The first-in-human Phase 1 study demonstrated that RMC-4630 is a potent, selective inhibitor of SHP2, which appears to be an important regulator of growth signals for cancer cells. RMC-4630 exhibited anti-tumor activity in cancers harboring KRASG12C, KRASG12D, NF1 loss of function and BRAF Class 3 mutations. Based on these findings, four targeted therapy combination studies are currently underway, including combinations of RMC-4630 with the KRASG12C inhibitor sotorasib, the checkpoint inhibitor pembrolizumab and the MEK inhibitor cobimetinib.

CAR T cell therapy reshapes tumor microenvironment in glioblastoma
Time: April 12 from 2:05 to 2:15 p.m. EDT
This translational research uses murine models and patient samples to evaluate how CAR T cell therapy reshapes the tumor microenvironment to promote host anti-tumor immune responses in glioblastoma. Christine Brown, Ph.D., deputy director of the T Cell Therapeutics Research Laboratory at City of Hope, and her colleagues look at IL13Rα2-targeted CAR T cells for the treatment of glioblastoma and demonstrate that CAR T cell treatment of mice with glioblastoma alters the tumor immune landscape, activates myeloid cells within tumors and induces innate T cell memory responses. These studies establish that CAR T cell therapy has the potential to reshape the microenvironment of solid tumors, potentially activating innate, adaptive immunity. Cancer Discovery recently accepted this research for publication.

CAR NK therapy directed against pancreatic cancer
Time: April 10, 8:30 a.m. to 11:59 p.m. EDT
This late-breaking poster presentation led by City of Hope’s Michael Caligiuri, M.D., and Jianhua Yu, Ph.D., presents a potent human chimeric antigen receptor (CAR) natural killer (NK) cell therapy against pancreatic cancer. About 60-80% of pancreatic cancer express prostate stem cell antigen. The scientists developed CYTO NK-203 to spontaneously kill both liquid and solid tumors in animal models using human umbilical cord NK cells that are transduced with CAR. The research suggests that this biopharmaceutical may be able to prolong survival against pancreatic tumor cells without side effects, at least in animal models. CYTO NK-203, which was licensed to CytoImmune Therapeutics Inc., is expected to move into clinical trials at City of Hope within 12 months, Caligiuri said.

Neighborhood disadvantage linked to aggressive non-small cell lung cancer
Time: April 10 from 8:30 a.m. to 11:59 p.m. EDT
City of Hope’s Loretta Erhunmwunsee, M.D., looked at the association of neighborhood disadvantage and the biology of aggressive non-small cell lung cancer. Non-small cell lung cancer has a disproportionately higher incidence and mortality rate in marginalized communities, who often reside in neighborhoods with adverse conditions influenced by economic, housing, education, transportation and environmental factors. Researchers looked at 426 non-small cell lung cancer patients treated at City of Hope and found that those who lived in disadvantaged neighborhoods were more likely to have a somatic KRAS mutation — a mutation that is associated with lower survival. This relationship was consistent even when smoking status and pollution were considered and suggests neighborhood disadvantage may be an important determinate of aggressive non-small cell lung cancer biology, possibly explaining why marginalized individuals have worse outcomes.

Predictors of clonal immune responses in colorectal cancer
Time: April 10 from 8:30 a.m. to 11:59 a.m. EDT
Stephen Gruber, M.D., Ph.D., M.P.H., director of City of Hope’s Center for Precision Medicine, studied clinical and epidemiologic predictors of clonal immune responses in colorectal cancer to better understand what causes diverse immune responses. He and his colleagues found that the use of statins and daily aspirin for more than five years prior to when a patient was diagnosed with colon cancer was strongly associated with the quality and behavior of the immune cells (T cells) within the tumor itself. Their research suggests that adaptive immune response may be linked to modifiable factors. Having a better understanding of the mechanisms that regulate immune responses in colorectal cancer may have implications for chemoprevention and immunotherapy.

On April 9, 2021 Nuvo Pharmaceuticals Inc. (TSX:MRV; OTCQX:MRVFF) d/b/a Miravo Healthcare (Miravo or the Company), a Canadian focused healthcare company with global reach and a diversified portfolio of commercial products, reported Jesse Ledger, Miravo’s President & Chief Executive Officer and Mary-Jane Burkett, Miravo’s Vice President & Chief Financial Officer will be presenting at upcoming investor conferences (Press release, Nuvo Pharmaceuticals, APR 9, 2021, View Source [SID1234580415]).

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Bloom Burton & Co. Healthcare Investor Conference

The Bloom Burton & Co. Healthcare Investor Conference brings together U.S., Canadian and international investors who are interested in the latest developments in the Canadian healthcare sector. Attendees will have an opportunity to obtain corporate updates from the premier Canadian publicly traded and private companies through presentations and private meetings.

Miravo Healthcare Presentation

DATE: Wednesday, April 21st, 2021
TIME: 10:00 a.m. EST
LINK: Conference Registration

Planet MicroCap Showcase

The Planet MicroCap Showcase VIRTUAL EVENT brings together the most promising companies and the top dealmakers in MicroCap Finance for three (3) days of company presentations, 1:1 meetings and educational panels in The Premier Virtual Event in MicroCap Finance.

Miravo Healthcare Presentation

DATE: Thursday, April 22nd, 2021
TIME: 10:00 a.m. EST
LINK: Miravo Presentation

On April 9, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported the most advanced asset arising from their joint venture with Exscientia has entered human clinical trials (Press release, Evotec, APR 9, 2021, View Source;announcements/press-releases/p/evotec-and-exscientia-announce-start-of-human-clinical-trials-of-novel-immuno-oncology-drug-6045 [SID1234577769]). The A2a receptor antagonist, which is in development for adult patients with advanced solid tumours, was co-invented and developed between Exscientia and Evotec, including application of Exscientia’s next generation 3-D evolutionary AI-design platform, Centaur Chemist. The drug candidate has potential for best-in-class characteristics, with high selectivity for the target receptor, bringing together potential benefits of reduced systemic side effects as well as minimal brain exposure to avoid potential undesired centrally-mediated side effects.

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Tumour cells produce high levels of adenosine, a molecule that helps them escape immune system detection by binding to the A2a receptor on cancer-fighting T-cells, reducing T-cell ability to eliminate disease. Therefore, this highly selective A2a receptor antagonist is being investigated for its ability to prevent adenosine from binding to the T-cell receptor and potentially promote anti-tumour T-cell activity.

Dr Craig Johnstone, Chief Operating Officer of Evotec, commented: "We highly value our ongoing partnership with Exscientia, which has been highly collaborative and productive in every respect. We are therefore delighted to announce the start of clinical development of our co-owned A2a antagonist with Exscientia in the hope that the fruits of our collaboration can bring potential benefits to patients in the future."

Prof. Andrew Hopkins, CEO and founder of Exscientia, said: "We set ambitious therapeutic objectives for this project, especially high selectivity for the A2a receptor and central nervous system (CNS) sparing properties, in order to reduce the likelihood of potential side effects. Even with these challenging objectives, we were able to discover our candidate molecule within 8 months of project initiation."

Exscientia will lead further clinical development of the molecule and Evotec will retain co-ownership rights throughout clinical development.