On March 28, 2018 Moleculin Biotech, Inc. (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported its financial results for the year ended December 31, 2017 (Press release, Moleculin, MAR 28, 2018, View Source [SID1234525040]). Additionally, the Company announced potential upcoming milestones and recent corporate developments.

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Management Discussion
Walter Klemp, Chairman and CEO of Moleculin, said, "We continued to make significant progress in developing Moleculin’s distinctive cancer treatment technologies during 2017. We firmly believe that all three of our highly differentiated technologies have breakthrough potential in effectively treating various cancers. From those three core technologies, we now have six potential drug candidates, two of which we expect will commence clinical trials in 2018, with the possibility of a third before the end of the year.

"Our potentially disruptive technologies include Annamycin, a chemotherapy agent that is active against multidrug resistant tumor cells and has been designed to be non-cardio toxic (unlike currently approved drugs in this class); immuno-stimulating STAT3 inhibitors WP1066 and WP1732 that target glioblastoma and pancreatic cancer; and WP1122, an inhibitor of glycolysis that has been shown in preclinical testing to effectively block the energy supply required by cancer cells and effectively starves the cancer cells to death. Our diverse development portfolio gives Moleculin what I like to call multiple shots on goal."

The Company submitted an application in October 2017 for a Clinical Trial Authorization ("CTA") for Annamycin in Poland. Having met all the requirements, the Ethics Committee in Poland approved the Phase I/II trial of Annamycin for the treatment of relapsed or refractory acute myeloid leukemia ("AML") in December 2017. In March the Company received requests for and provided additional information to the Polish National Office. It expects a response from the Polish National Office in the first half of 2018 and at the earliest mid-April 2018. The start of clinical trials in Poland remains subject to confirmation and approval of the CTA by the Polish National Office. The Company can provide no assurance that it will receive such confirmation on a timely basis, if at all.

In addition, the Company continues to recruit and contract clinics both in the United States and Poland. In the U.S., the Company has one site — University Hospitals Cleveland Medical Center ("UHCMC") — recruiting patients and enrollment has begun. The Company can provide no assurance that it will continue enrollments or begin treatment on a timely basis, if at all.

Mr. Klemp continued, "Additionally, this past December we announced that a physician-sponsored Investigational New Drug ("IND") application for a Phase I trial of Moleculin’s WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma was allowed by the U.S. Food and Drug Administration ("FDA"). This will be our second drug in clinical trials. The trial will be conducted at the MD Anderson Cancer center to evaluate safety and efficacy. We believe WP1066 represents a new class of oncology drugs able to fight tumors on two fronts by directly inhibiting cell signaling supporting tumor activity, and independently stimulating a natural immune response. This constitutes a new approach to treating brain tumors and tumor metastasis to the brain.

"We also intend to request a clinical trial authorization in Poland for WP1220 for the topical treatment of Cutaneous T-Cell Lymphoma (CTCL), which we expect will become our third compound in clinical trials in 2018. WP1220 is one of our patented STAT3 inhibitors designed to be compatible with topical formulations and was selected based on its preclinical activity in CTCL cell lines and based on the need for better topical treatments for skin cancer.

"As we look ahead to 2019 and beyond, we are excited about a new molecule that we recently licensed from MD Anderson — WP1732 — that shares many of the same characteristics of WP1066, especially its ability to inhibit activated STAT3, which is widely considered a key transcription factor involved in the development and progression of tumors. WP1732 has demonstrated significantly different organ distribution in animal models, suggesting it could be especially well-suited to target systemic solid tumors including pancreatic cancer, one of the most deadly and difficult to treat.

"An important attribute of WP1732 is that it is more water-soluble than WP1066. So, while we have been focused on oral delivery of WP1066, WP1732 is ideally suited to intravenous ("IV") administration, which makes the delivery of the drug potentially more convenient and efficacious. We’ve already started the process of preparing the preclinical data necessary for an IND for WP1732 and we hope to have that preparation completed in 2018.

"I also want to acknowledge the outstanding Scientific Advisory Board that is part of the Moleculin brain trust. Waldemar Priebe, PhD., a Founder of Moleculin and the Company’s Founding Scientist, leads a team of world renown experts in various cancer fields that includes John Paul Waymack, MD; Elihu Estey, MD; and Jorge Cortes, MD. Together with our two Chief Medical Officers, Robert Shepard, MD (Annamycin), and Sandra Silberman, MD (New Products), their expertise and guidance have enabled us at Moleculin to successfully proceed in the development of our highly differentiated compounds. Our expectation is that 2018 will see significant progress in advancing our portfolio of unique cancer treatments," concluded Mr. Klemp.

Fourth Quarter Highlights and Recent Corporate Developments
Moleculin Announces Grant-Funded Collaboration to Expand Understanding of New Discovery – March 20, 2018, the Company announced it has entered into a collaboration with a team of scientists in Poland who have received a $300,000 research grant to expand the understanding of how Moleculin’s leading STAT3 inhibitor WP1066 and the Company’s newly discovered drug candidate, WP1732, create a blockade of transcription factor STAT3 leading to tumor cell death and immune-stimulating effects.

Moleculin Announces Pricing of $9 Million Registered Direct Offering – February 16, 2018, the Company announced that it has entered into a definitive agreement with institutional investors for a registered direct offering of securities with gross proceeds of approximately $9 million.

Moleculin Announces Breakthrough Discovery of a New Molecule for Cancer Treatment – February 15, 2018, the Company announced that, pursuant to its continued collaboration with MD Anderson it has developed and licensed what it believes, based on preclinical testing, is a major breakthrough in its effort to develop a new cancer treatment that selectively kills highly resistant tumors. Specifically, the Company has preclinical evidence to suggest it is capable of influencing a process known as ‘ubiquitination’ to block the activated form of STAT3, an important oncogenic transcription factor. The lead molecule resulting from this new discovery is called WP1732 and it not only appears to share the same key mechanistic properties with WP1066, it has markedly different organ distribution and its dramatically increased solubility makes it ideal for administration via standard IV injection. Importantly, preclinical testing has also shown that WP1732’s properties make it a promising candidate for treating pancreatic cancer.

Moleculin Announces Collaboration with Emory University to Develop Novel Treatment of Pediatric Brain Cancer – February 13, 2018, the Company announced it has entered into an agreement with Emory University to enable expanded cancer research on Moleculin’s WP1066 molecule for the possible treatment of medulloblastoma, a pediatric malignant primary brain tumor. Physician-scientists at Emory University and Children’s Healthcare of Atlanta have requested support to continue research aimed at the development of a novel treatment of medulloblastoma using WP1066 and Moleculin has agreed to supply them with a pure form of WP1066 for preclinical testing for the potential future treatment of patients with the disease. Emory studies so far have indicated that medulloblastoma may be particularly vulnerable to the ability of WP1066 to block the activated form of STAT3, a key signaling protein believed to contribute to the growth and survival of many tumors, including medulloblastoma.

Moleculin Announces Activity with Pancreatic Cancer Drug – February 7, 2018, the Company announced it has been able to show promising tumor suppression activity with its inhibitor of glycolysis, WP1122. The Company’s glycolysis inhibitors have shown a remarkable affinity for concentrating in the pancreas and has solid data showing the ability of WP1122 to inhibit pancreatic tumor growth in mice.

Leading Leukemia Experts Join Moleculin’s Science Advisory Board – January 17, 2018, the Company announced the expansion of its Science Advisory Board to include Drs. Jorge Cortes and Elihu Estey.

Jorge Cortes, M.D., is deputy chair and professor of medicine in the Department of Leukemia at MD Anderson Cancer Center where he directs the CML and AML Programs. Dr. Cortes received his medical degree in 1986 from the Universidad Nacional Autonoma de Mexico, and has been at MD Anderson since 1991. Dr. Cortes, whose clinical interest focuses on new drug development and the management of patients with myelodysplatic syndromes, acute and chronic leukemias, and myeloproliferative disorders, has authored over 900 peer-reviewed medical publications in top-tier journals including New England Journal of Medicine, Lancet Oncology, Lancet Hematology, Journal of Clinical Oncology, Leukemia, Blood and many others.

Elihu Estey, M.D., is a Professor of Medicine in the Division of Hematology at the University of Washington School of Medicine and a Full Member and Director of AML Clinical Research (non-transplant) Clinical Research Division, Fred Hutchinson Cancer Research Center. Dr. Estey has built a distinguished career in cancer research approaching 40 years of active clinical practice with AML patients, providing mentorships for many physicians that have risen to prominence in AML, lectured globally to professional audiences on cancer research and published more than 700 articles on hematologic malignancies, specifically on AML. Additionally, Dr. Estey serves on the European Leukemia Net (ELN) guidelines committee for AML and has served as an advisor for AML studies to the Oncology Drugs Advisory Committee ("ODAC") of the FDA.

Moleculin Expands Leukemia Development Portfolio with Immuno-Stimulating STAT3 Inhibitor – January 10, 2018, the Company announced it has expanded the Company’s development pipeline for the treatment of AML with an immuno-stimulating STAT3 inhibitor. Leading experts in the treatment of AML, Dr. Jorge Cortes and Dr. Sanjay Awasthi requested the Company to expand its clinical research to include WP1066, an immuno-stimulating agent and STAT3 inhibitor, to increase therapeutic options for AML patients. This would potentially be complementary and synergistic with Annamycin and existing first line treatments.

Moleculin Announces Polish Approval for Leukemia Clinical Trial – December 21, 2017, the Company announced that the Ethics Committee in Poland has approved the Company’s Phase I/II clinical trial of Annamycin for the treatment of relapsed or refractory AML.

Moleculin’s WP1066 Drug gets FDA Brain Tumor IND Clearance – December 5, 2017, the Company announced the physician-sponsored IND application for a Phase I trial of Moleculin’s drug WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma has been allowed by the FDA. WP1066 is the second of Moleculin’s drugs to enter clinical stage and represents a new class of oncology drugs able to fight tumors on two fronts by directly inhibiting cell signaling and independently stimulating a natural immune response. This IND was sponsored by Dr. Amy Heimberger, who will serve as the principal investigator for the Phase I trial at MD Anderson Cancer Center to evaluate safety and efficacy.

Moleculin Appoints Dr. Sandra Silberman as Chief Medical Officer – New Products – November 8, 2017, the Company announced the appointment of Dr. Sandra Silberman as Chief Medical Officer ("CMO") in charge of New Products.

Moleculin Announces MD Anderson has Filed an IND with the FDA on its Drug WP1066 for the Treatment of Brain Tumors – November 1, 2017, the Company announced that responses have been submitted to FDA requests for additional information relating to the physician-sponsored IND application to study WP1066 as a potential treatment for brain tumors.

Moleculin Requests Authorization from the Polish Government to Advance Annamycin – October 24, 2017, the Company announced that it has submitted its request for CTA in Poland which, if allowed, will enable a clinical trial to study Annamycin for the treatment of relapsed or refractory AML in Poland. This will be in addition to the previously announced allowance of Moleculin’s IND filing with the FDA.

Moleculin Announces 14 Qualified Clinical Sites Requesting Participation in Annamycin Trial – October 18, 2017, the Company announced that 14 qualified cancer clinics have requested to participate in its clinical trial to study Annamycin for the treatment of relapsed or refractory AML.

Moleculin Announces Strategic Collaboration to Develop Immuno-stimulating Drug – October 11, 2017, the Company announced that it has entered into an agreement to collaborate with the University of Bergen to expand research on WP1066 and early indications of a possible dual ability to increase immune system response to tumors while also suppressing tumor cell proliferation tumor cell and survival.

Moleculin Signs Agreement with First Hospital for Annamycin Trials – October 3, 2017, the Company announced it has entered into an agreement with the first of several hospitals desiring to become treatment sites for its clinical trial to study Annamycin for the treatment of relapsed or refractory AML.

Moleculin Announces FDA Approval of Annamycin IND – September 26, 2017, the Company announced that the FDA has allowed Moleculin’s IND for the study of Annamycin in relapsed or refractory AML to proceed. This allows Moleculin to begin clinical trials of Annamycin in the U.S.

Anticipated Milestone Potential Timeframe
Announcement that our IND for Annamycin has become effective and that we may begin clinical trials Accomplished
Initial IRB (Institutional Review Board) approvals and site initiations of various clinical sites participating in our Phase I/II clinical trial of Annamycin Accomplished and ongoing through Second Half of 2018
Establishment of a new RP2D for Annamycin Second Half of 2018
A clinician sponsored IND for WP1066 for treatment of adult brain tumors moving forward IND Accomplished; Trial expected to begin First Half of 2018
Announcement of initial Clinical Data for Annamycin trial 2018
Announcement of further benefits of our sponsored research agreement with MD Anderson Accomplished and Ongoing into 2019
Announce CTA for WP1220 for the treatment of cutaneous T-cell lymphoma (CTCL) 2018
Announce WP1122 and WP1732 move into preclinical work 2018
Announce the fourth drug approved for clinical trial 2019
Financial Results for the Year Ended December 31, 2017
Research and Development Expense. Research and development (R&D) expense was $4.5 million and $1.5 million for the years ended December 31, 2017 and 2016, respectively. The increase in R&D of approximately $3.0 million mainly represents an increase of approximately: $2.0 million associated with developing and testing drug product as we prepared for clinical trials; $0.4 million related to an increase in R&D headcount and associated payroll costs; $0.3 million for sponsored research and related expenses; and $0.3 million associated with license fees. The increase in R&D headcount mainly represents the associated costs of increasing the commitments of the Company’s part-time employees and the addition of a second Chief Medical Officer – New Products. These all are a reflection of the increased clinical and pre-clinical activity for its drug portfolio as compared to 2016.

General and Administrative Expense. General and administrative (G&A) expense was $4.1 million and $2.4 million for the years ended December 31, 2017 and 2016, respectively. The increase in G&A of approximately $1.7 million was mainly attributable to: (a) the increase in headcount and associated payroll costs, including additional stock-based compensation expense of $1.0 million; (b) approximately $0.4 million in legal, accounting, consulting, and other professional expenses; (c) $0.2 million in insurance expense; and (d) approximately $0.1 million in occupancy, office and other costs. These increases reflect the increase in support of the Company’s clinical activity described above as compared to 2016.

Net Loss. The net loss for the twelve months ended December 31, 2017 was $9.8 million, which included non-cash expenses of approximately $0.7 million, which was comprised almost completely of stock-based compensation.

Liquidity and Capital Resources
As of December 31, 2017, we had $7.7 million in cash. During 2017, via an equity offering in February of 2017 (the February 2017 Offering), the Company’s at-the-market issuance agreement (ATM), and the exercise of warrants associated with the February 2017 Offering, the Company issued 7.2 million shares of common stock and received $10.1 million in net proceeds. Subsequent to year-end the Company entered into a Purchase Agreement with certain Investors for the sale of 4,290,000 shares of its common stock at a purchase price of $2.10 per share. Concurrently with the sale of the common shares, pursuant to the Purchase Agreement, the Company also sold warrants to purchase 2,145,000 shares of common stock, which have an exercise price of $2.80 per share. This sale of common shares and warrants generated aggregate gross proceeds of approximately $9.0 million with net proceeds approximating $8.3 million (February 2018 Offering). The Company believes that its existing cash and cash equivalents as of December 31, 2017 along with the cash generated by the February 2018 Offering, will be sufficient to fund its planned operations into the first quarter of 2019. Such plans are subject to change depending on clinical enrollment and regulatory progress and the use and supply of drug product.

On March 27, 2018 Bristol-Myers Squibb Company (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) accepted its supplemental Biologics License Application (sBLA) for Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of adults with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan (Press release, Bristol-Myers Squibb, MAR 27, 2018, View Source [SID1234525385]). The FDA granted the application priority review and, in February 2018, granted the combination Breakthrough Therapy Designation for this potential indication, recognizing the need for new treatment approaches in this patient population. The FDA action date is July 10, 2018.

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"The FDA acceptance of this application with priority review reinforces our belief in the potential of the Opdivo plus Yervoy combination to treat patients with previously treated metastatic colorectal cancer defined by MSI-H or dMMR biomarkers, and is a result of our longstanding commitment to the exploration of I-O/I-O combinations for patient populations with high unmet need," said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. "We look forward to working with the FDA with the goal of bringing this combination to these colorectal cancer patients."

This application is based on data from the ongoing Phase 2 CheckMate -142 study evaluating the Opdivo and Yervoy combination in previously treated patients with MSI-H or dMMR mCRC. Data from this study were presented in January at the 2018 Gastrointestinal Cancers Symposium and published simultaneously in the Journal of Clinical Oncology.

The FDA’s Breakthrough Therapy Designation is a process intended to enable timely patient access by expediting the development and review of medicines for serious conditions where preliminary clinical evidence indicates a substantial improvement over available therapies on one or more clinically significant endpoints.

About MSI-H or dMMR Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. In the U.S., CRC is the third most common cancer with more than 140,000 new cases expected to be diagnosed annually, and the third leading cause of cancer-related deaths among men and women combined.
DNA mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 15% of CRC patients and 4-5% of metastatic CRC patients have MSI-H or dMMR biomarkers. Patients with MSI-H or dMMR metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis. Routine testing to confirm MSI-H or dMMR status should be conducted for all CRC patients.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are advancing the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. Through our leading translational capabilities, we are pioneering immune biology research and identifying a number of potentially predictive biomarkers, including PD-L1, TMB, MSI-H/dMMR and LAG-3, advancing the possibility of precision medicine for more patients with cancer.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO
OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.
Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, and myasthenic syndrome.

If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate study in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In patients receiving OPDIVO as a 60-minute infusion prior to the infusion of YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO
glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in at least 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in at least 2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO-treated patients.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). The most common adverse reactions (≥20%) in patients who received OPDIVO as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, and abdominal pain.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).
Checkmate Trials and Patient Populations

Checkmate 067–advanced melanoma alone or in combination with YERVOY (ipilimumab); Checkmate 037 and 066–advanced melanoma; Checkmate 017–squamous non-small cell lung cancer (NSCLC); Checkmate 057–non-squamous NSCLC; Checkmate 025–renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 040–hepatocellular carcinoma, Checkmate 238–adjuvant treatment of melanoma.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd. (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On March 27, 2018 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported that Paul Chaplin, President & Chief Executive Officer will provide a corporate presentation at Needham & Company’s 17th Annual Healthcare Conference in New York City on Tuesday, March 27, 2018 at 4:00 PM EDT (Press release, Bavarian Nordic, 27 27, 2018, View Source [SID1234525016]).

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A live and archived webcast of the presentation will be available at http://bit.ly/2DZQgOi.

Contacts
U.S.: Seth Lewis, Vice President, Investor Relations. Phone: +1 978 341 5271
Europe: Rolf Sass Sørensen, Vice President Investor Relations & Communications. Phone +45 61 77 47 43

On March 28, 2018 Tusk Therapeutics, an immuno-oncology company focused on developing immune-modulating therapeutics by targeting immune cells in cancer, reported that it will deliver an oral presentation and three poster presentations at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place from 14th – 18th April 2018 at McCormick Place North/South, Chicago, Illinois, US (Press release, Tusk Therapeutics, MAR 27, 2018, View Source [SID1234525041]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Dr. Sergio Quezada, Group Leader and Cancer Research UK Senior Research Fellow at The UCL Cancer Institute, and Chairman of Tusk Therapeutics’ Scientific Advisory Board, will deliver the oral presentation at 10.30am on Monday 16th April. The presentation will focus on Tusk Therapeutics’ first-in-class anti-CD25 antibody programme which is built on novel biology discovered by Tusk Therapeutics in collaboration with Dr. Quezada and his team at University College London. Tusk Therapeutics, Cancer Research UK (via its Commercial Partnerships Team) and UCL announced in 2017, an exclusive licensing and collaboration deal to develop and commercialise antibody-based therapeutics against CD25.

Commenting on the presentations, Luc Dochez, Chief Executive Officer of Tusk Therapeutics said: "We are excited to be presenting data at the upcoming AACR (Free AACR Whitepaper) meeting, in particular, to share data on the unique mechanism behind our anti-CD25 programme. It is well accepted that regulatory T-cells play an important role in immune-suppression in cancer but, thus far, nobody has been able to target Tregs effectively. Based on the pre-clinical proof-of-concept data generated in collaboration with Cancer Research UK and University College London, we

have shown that our novel approach can successfully target Tregs and therefore we believe that Tusk Therapeutics’ anti-CD25 antibody could become an important player in the immuno-oncology field."

​The full list of abstracts accepted for presentation at this year’s AACR (Free AACR Whitepaper) Meeting are detailed below:

Oral Presentation

Title: Targeting regulatory T cells for therapeutic gain: Means and mechanisms
Presenter: Dr. Sergio A. Quezada. University College London Cancer Institute

Session: In Vivo Monitoring of Immunotherapy Responses
Date & Time: April 16, 2018, 10:30 AM – 10:55 AM
Location: N Hall C – McCormick Place North (Level 1)

Poster Presentations

Title: Generation of first-in-class anti-CD25 antibodies depleting Treg without interfering with IL2 signalling for cancer therapies

Abstract: 2787
Session: Therapeutic Antibodies, Including Engineered Antibodies 2

Date & Time: April 16, 2018, 1:00 PM – 5:00 PM
Location: Section 34

Title: A novel approach to deplete Treg cells using non-IL-2 blocking anti-CD25-targeting antibodies leads to complete rejection of established tumors

Abstract: 3143

Session: Immune Cells in the Microenvironment

Date & Time: April 17, 2018, 8:00 AM – 12:00 PM
Location: Section 5

Title: A best in class anti-CD38 antibody with antitumor and immune-modulatory properties

Abstract: 3812

Session: Therapeutic Antibodies, Including Engineered Antibodies 3

Date & Time: Apr. 17, 2018, 8:00 AM – 12:00 PM

Location: Section 34

Full abstracts are available online at www.aacr.org.

For further information, please contact:

Tusk Therapeutics

Luc Dochez, Chief Executive Officer

[email protected]

Media Enquiries:

Consilium Strategic Communications

Julia Wilson, Lindsey Neville

+44 (0) 203 709 5708

[email protected]

On March 27, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), has received SAKIGAKE Designation for the treatment of HER2-positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW) (Press release, Daiichi Sankyo, MAR 27, 2018, View Source [SID1234525386]).

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"There are no HER2-targeting treatment options currently available for patients with HER2-positive gastric cancer whose tumors are no longer controlled by trastuzumab," said Koichi Akahane, PhD, MBA, Executive Officer, Head of Oncology Function, R&D Division, Daiichi Sankyo. "We look forward to working closely with the Japan Ministry of Health, Labour and Welfare under the terms of the SAKIGAKE program to accelerate the development of DS-8201 particularly since Japan has one of the highest incidence rates of gastric cancer worldwide."

The SAKIGAKE Designation System promotes R&D in Japan, driving early practical application for innovative pharmaceutical products, medical devices and regenerative medicines. As a designated medicine under the SAKIGAKE Designation system, DS-8201 will have prioritized consultation, a dedicated review system to support the development and review process, as well as reduced review time from the normal 12 to 6 months.

"We are pleased that DS-8201 has received SAKIGAKE Designation for advanced HER2-positive gastric cancer, which follows the Breakthrough Therapy and Fast Track designations granted by the U.S. FDA for HER2-positive metastatic breast cancer," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These three designations for DS-8201 underscore our commitment to active and close collaborations with health authorities in order to potentially bring DS-8201 as a new treatment option to patients with different types of HER2-expressing cancers worldwide as quickly as possible."

SAKIGAKE Designation was granted based on the results of an ongoing phase 1 study assessing the safety, tolerability and preliminary efficacy of DS-8201. Updated preliminary results of DS-8201 from a subgroup analysis of HER2-positive advanced gastric cancer previously treated with trastuzumab and chemotherapy were recently presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.1

Unmet Need in Gastric Cancer
Gastric cancer is the fifth most common cancer worldwide, with nearly one million new cases reported in 2012.2 Approximately half of all gastric cancer cases occur in eastern Asia, with Japan having the third highest incidence rate worldwide.2,3 Gastric cancer is the third leading cause of cancer-related death worldwide, and the second leading cause of cancer-related death in Japan.2,4

Approximately one in five gastric cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells.5 HER2-expressing gastric cancer is an area of unmet medical need as advances in the treatment of the disease have been limited, largely due to its genetic complexity and heterogeneity.6 Currently, there are no approved HER2-targeting therapy options for patients with HER2-positive advanced gastric cancer after treatment with trastuzumab.

About DS-8201
DS-8201 is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in pivotal phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), pivotal phase 2 development for HER2-positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01), phase 2 development in advanced colorectal cancer and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science Franchise, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: DS-8201, an antibody drug conjugate (ADC) for HER2-expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/
refractory acute myeloid leukemia (AML) with FLT3-ITD mutations; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com