/home/bill/PROJECTS/Investments/0_Oncolytics reference.txt www.BillHowell.ca 25Jun2020 initial split off "Oncolytics notes.txt ******** Trial partners & agreements Incyte, triple negative Breast Cancer Trial 25Jun2020 anti-PD-1 checkpoint inhibitor retifanlimab (INCMGA00012) Adlai Nortye pelareorep breast cancer, done Phase 2, Chinese approval for Phase 3 http://www.adlainortye.com/en_product.php Hangzhou Economic & Technological Development Area, 310018, P.R.China (near Shanghai?) Adlai Nortye pelareorep breast cancer, done Phase 2, Chinese approval for Phase 3 (see below) Japanese Oncolys https://www.oncolys.com/en/ https://www.oncolys.com/en/pipeline/ maybe Pfizer Ibrance in future? 11Jun2020 Chugai 50 GYen deal with Oncolys China - 10 oncolytic viruses ******* Competitive Landscape https://en.wikipedia.org/wiki/List_of_largest_biomedical_companies_by_revenue 2019 sales G$ 82.06 Johnson&Johnson,Janssen NYSE: JNJ a Benevir Undisclosed –preclinical 63.85 Roche SIX: ROG s ONC Tecentriq® 60.18 Sinopharm SEHK: 1099 oops - ONC link here? couldn't find for Adlai Nortye 51.75 Pfizer NYSE: PFE s ONC Ibrance? s ONC KGaA's Bavencio® 48.02 Bayer FWB: BAYN n/a 47.45 Novartis NYSE: NVS n/a 46.84 Merck NYSE: MRK s ONC KGaA's Bavencio® s ONC Keytruda® a Viralytics Type A21 Coxsackievirus–phase 1b p Vyriad Measles phase 1/2 43.92 GlaxoSmithKline LSE: GSK n/a 39.28 Sanofi NYSE: SNY n/a 33.27 AbbVie NYSE: ABBV p TurnstoneBio Rhabdovirus phase 1/2 Jun2020 HUGE 7.3G$ Fed bond purchase!! 31.90 Abbott Laboratories NASDAQ: ABT n/a 30.73 Takeda Pharmaceutical TYO: 4502 l TurnstoneBio RIVAL-01-preclinical 26.15 Bristol-Myers Squibb NASDAQ: BMY s ONC Opdivo® s ONC->Adlai Nortye Paclitaxel-phase3 p PsiOxus Adenovirus–phase 1 25.54 Thermo Fisher Scient NYSE: TMO n/a 24.38 AstraZeneca LSE: AZN n/a 23.40 Amgen NASDAQ: AMGN a Biovex HSV–phase 3 22.45 Gilead Sciences NASDAQ: GILD n/a 16G€ Boehringer Ingelheim private a ViraTherapeutics VSV preclinical s study a acquisition p partner l license Boehringer Ingelheim - lists parent company revenues Jansen or Janssen(J&J) ?? +--+ Small fry pharma sales... ?? Adlai Nortye, China 00.47 Incyte NASDAQ: INCY ?s ONC retifanlimab, 00.01 Oncolys, Japan +-----+ https://ssl4.eir-parts.net/doc/4588/tdnet/1793691/00.pdf 2019 financial statement 1,303 MY * 0.0093 Y/$ = +-----+ http://www.adlainortye.com/en_about.php "Sinopep Pharmaceutical" was established in 2004. Raising $53 million in Series B Round of financing in June, 2018. http://www.adlainortye.com/en_newsdetail.php?cid=69&id=113 Adlai Nortye Receives NMPA Approval for Pelareorep Phase III Clinical Trials 2019-03-22 16:45:26 HANGZHOU, China, -- March 21, 2019 -- Adlai Nortye Ltd. ("Adlai Nortye"), a global clinical-stage biopharmaceutical company today announced that it has received a clearance from the National Medical Products Administration (NMPA) of China for initiating the open-label, randomized, multicenter, global phase III clinical trial for pelareorep (AN1004) in combination with paclitaxel in patients with advanced/ metastatic breast cancer in China. Pelareorep is a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. In the presentation of pelareorep clinical data, additional randomized phase II data in metastatic breast cancer demonstrates doubling (21.8 months vs. 10.8 months) of overall survival in Hormone Receptor Positive (ER+PR+)/HER2- patients. Pelareorep has received Fast Track designation and Special Protocol Assessment Agreement for Phase III Clinical Trial from FDA for the treatment of metastatic breast cancer. Carsten Lu, Chairman and CEO of Adlai Nortye said: " The incidence of breast cancer ranks No. 1 among female malignant tumors in China. Adlai Nortye focuses on discovering and developing innovative treatments in cancer patients, trying to transform cancer into a chronic disease condition even cure the cancer disease. The NMPA gave detailed and constructive guidance to the pelareorep phase III clinical program. We are very pleased and encouraged by the result. We will launch the clinical trial to join our global partner Oncolytics Biotech Inc. when they initiate their phase III registration study. We will continue to bring more options to cancer patients." https://www.oncolyticsbiotech.com/press-releases/detail/389/oncolytics-biotech-inc-and-adlai-nortye-enter-into-usd Oncolytics Biotech® Inc. and Adlai Nortye Enter into USD $86.6 Million Regional Licensing Agreement for REOLYSIN® Download as PDF November 16, 2017 Regional license covers China, Hong Kong, Macau, Singapore, South Korea and Taiwan Oncolytics to receive upfront, licensing fee and milestone payments to support phase 3 registration study of USD $21.2 million, and eligible to receive up to an additional USD $65.4 million upon achievement of clinical, regulatory and commercialization milestones Upon Adlai Nortye's commercialization of REOLYSIN®, Oncolytics is eligible to receive double digit royalty payments +-----+ https://en.wikipedia.org/wiki/Janssen_Pharmaceutica Janssen Pharmaceutica janssenpharmaceuticalsinc.com Janssen Pharmaceutica is a pharmaceutical company headquartered in Beerse, Belgium and owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceutica was purchased by New Jersey-based American corporation Johnson & Johnson, and became part of Johnson & Johnson Pharmaceutical Research and Development (J&J PRD), now renamed to Janssen Research and Development (JRD), which conducts research and development activities related to a wide range of human medical disorders, including mental illness, neurological disorders, anaesthesia and analgesia, gastrointestinal disorders, fungal infection, HIV/AIDS, allergies and cancer. Janssen and Ortho-McNeil Pharmaceutical have been placed in the Ortho-McNeil-Janssen group within Johnson & Johnson Company. +-----+ https://www.tradingview.com/symbols/NASDAQ-INCY/Employees: 1456 Incyte Corp. is a biopharmaceutical company, which engages in the discovery, development and commercialization of proprietary therapeutics. Its portfolio includes compounds in various stages, ranging from preclinical to late stage development, and commercialized products such as JAKAFI (ruxolitinib), and ICLUSIG (ponatinib). The company was founded by Roy A. Whitfield in April 1991 and is headquartered in Wilmington, DE. >> HUGE stock ramp-up 2013-2016!! volatile since then +-----+ Boehringer Ingelheim boehringer-ingelheim.com C.H. Boehringer Sohn AG & Ko. KG is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical companies, and the largest private one.Wikipedia https://en.wikipedia.org/wiki/Boehringer_Ingelheim Headquartered in Ingelheim, it operates globally with 146 affiliates and more than 47,700 employees. Unlike most large pharmaceutical companies which are listed, the company is private and fully owned by the Boehringer, Liebrecht and von Baumbach families.[2] The company's key areas of interest are: respiratory diseases, metabolism, immunology, oncology and diseases of the central nervous system. €15.9 billion (2017)[1] 2018–onwards In April 2018 the company announced that it would launch an immuno-oncology partnership with OSE Immunotherapeutics worth up-to-$1.4 billion, focussing on developing OSE's late-preclinical-stage candidate OSE-172, a checkpoint inhibitor antibody designed to treat solid tumors.[28] In the same month Boehringer announced a partnership with Topas Therapeutics and their virus-based vectors.[29] In mid-September the company exercised its option to acquire viral cancer therapy developer, ViraTherapeutics, for €210 million ($245 million).[30] In March 2019 Boehringer announced it would acquire ICD Therapeutics.[31] In July, subsidiary company Boehringer Ingelheim Pharmaceuticals, Inc. announced it had acquired Amal Therapeutics SA, boostings the business' focus on cancer immunotherapy and vaccine treatments.[32] In May 2020, the business announced it would acquire Northern Biologics Inc. which focuses on therapeutic antibodies targeting tumours.[33] In June, the business announced it would sell off part of its stake in London-listed Hikma Pharmaceuticals (28 million out of a 40 million share holding) for around $800 million.[34] ******** ONCY Institutional shareholders https://fintel.io/so/us/oncy ONCY / Oncolytics Biotech, Inc. - Institutional Ownership and Shareholders >> one of the bloggers claims 250k+ shares >> Largest institutional : Two Sigma Advisers, Lp 150,700 shares Roche Holding AG engages in the diagnostics and prescription pharmaceuticals businesses in Switzerland, Germany, and internationally. Roche Holding AG has announced that Tecentriq in combination with chemotherapy (including Abraxane) meets primary endpoint of improved pathological complete response, regardless of PD-L1 status, as initial treatment for people with early triple-negative breast cancer. Xynomic Pharmaceuticals Holdings, Inc. is a clinical stage oncology-focused biopharmaceutical company. Its latest report announced the dosing of the first Chinese patient in its on-going global pivotal Phase 3 trial of Xynomic's abexinostat combined with pazopanib as a first- or second-line therapy against renal cell carcinoma (RCC) at Peking University Cancer Hospital & Institute. Dr. Jun Guo, Professor and Medical Director at Peking University Cancer Hospital & Institute, is the leading principal investigator for this trial in China. Can-Fite BioPharma Ltd. (NYSE American: CANF) is an advanced clinical stage drug development Company with a platform technology that is designed to address multibillion-dollar markets in the treatment of cancer, inflammatory disease and sexual dysfunction. Can-Fite has announced that the company has successfully concluded a meeting with the Scientific Advice Working Party (SAWP) of the European Medicines Agency (EMA) regarding Phase III development of its drug candidate Namodenoson in the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer. vk04982 6/13/20, 10:54 PM @Canadafan14 Thanks for your feedback. Price at the moment just does not make any sense. Major holders that have opened new positions in ONCY include Two Sigma Advisers, Lp, Creative Planning, Wedbush Securities Inc, Banco Bilbao Vizcaya Argentaria, S.a., Private Advisor Group, LLC, Advisor Group Holdings, Inc., BlackRock Inc., Fifth Third Bancorp, Bank Julius Baer & Co. Ltd, Zurich, and Cowen Prime Services LLC. - Which seems reasonably good. >> How did she get the names of investors?!!! *(see "https://fintel.io/so/us/oncy") ******** 17Jun2020 +-----+ https://www.benzinga.com/general/biotech/20/06/16261362/the-daily-biotech-pulse-glaxosmithkline-ideaya-strike-oncology-partnership-decision-day-for-merck GlaxoSmithKline Announces Strategic Partnership With IDEAYA In Synthetic Lethality GlaxoSmithKline plc GSK 1.26% and Ideaya Biosciences Inc IDYA 44.63% announced a strategic partnership in synthetic lethality, an emerging field in oncology, which included the latter's synthetic lethality programs MAT2A, Pol Theta and Werner Helicase. Both these programs are to reach clinical trials within the next three years, the companies said. According to the agreement, IDEAYA is to lead the MAT2A program through early clinical development and meet all costs before GlaxoSmithKline exercises options. Thereafter, IDEAYA will contribute 20% of the global development costs. In return, IDEAYA will receive a 50% U.S. profit share and ex-U.S. royalties for the MAT2A and Werner Helicase programs. In premarket trading Tuesday, GlaxoSmithKline shares were rising 1.69% to $41.41 and IDEAYA was rallying 101.12% to $18. See also: The Week Ahead In Biotech: FDA Decisions In The Cards For Merck, Epizyme, Evoke And Ultragenyx +-----+ https://d1io3yog0oux5.cloudfront.net/_d4c3d5008da1a96fbe2eb375fcc24f8e/oncolyticsbiotech/db/300/2426/pdf/5.08.20+-+Corporate+Presentation.pdf slide #5 - comparison Oncolytics versus competitors' oncolytic viruses Pelareorep & Competitive Advantages: dsRNA5 Other OV’s Intratumoral Delivery •Specialized delivery •Variable dose •Assured delivery to tumor Armed/Modified Virus •Customized handling (changes to standard of practice) •Biosafety Level 3 Pelareorep Intravenous Delivery •Ease of delivery •Standard dose •Accesses both primary and metastatic disease Unarmed/Unmodified Virus •No change to standard practice •Biosafety Level 2 Biomarkers •T cell clonality (measure by TCR Sequencing) •CEACAM6 (measured by immunostaining) •Predictive and prognostic Slide #28 Pharma’s Growing Interest in Oncolytic Viruses competitors' oncolytic viruses : 4 acquisitions, 3 partnerships, nothing for Oncolytics Partnerships and acquisitions were frequently preceded by an active research collaboration between the parties Co-Development Study •Co-development agreement with Pfizer/EMD Serono to evaluate Bavencio in 2L mBC Oncolytics or Investigator Sponsored Trials (IST’s) 4 ongoing combination studies with Merck, Roche & Bristol-Myers Squibb Monetize Certain Geographies Successful partnership with Adlai Nortye •China, Hong Kong, Macau, Singapore, South Korea and Taiwan Upfront and milestone payments of up to $86.6M •$21M in milestone payments largely under Oncolytics’ control, with double-digit royalties •$65M tied to potential development expansion Catalysts & Milestones Combination With Timing AWARE-1 breast cancer study: interim biomarker data (ESMO) Roche / Tecentriq® Q2 2020 Phase 1 NCI-9603 multiple myeloma study: interim data (ASCO)* Kyprolis® Q2 2020 Phase 2 NU 18I01second line pancreatic cancer study: Merck / Keytruda® Q2 2020 interim data (ASCO)* Phase 1 WINSHIP 4398-18 multiple myeloma study: interim data (ASH)* Bristol-Myers Squibb / Opdivo® Q4 2020 Phase2 NU 18I01second line pancreatic cancer study: final data*Merck / Keytruda® Q4 2020 * Guidance provided by principal investigator Anticipated Catalysts & Milestones Combination With Initiate phase 2 BRACELET-1 study in HR+ / HER2-mBC Pfizer & Merck KGaA / Bavencio® Phase 2 BRACELET-1 metastatic breast cancer study: interim safety update Pfizer & Merck KGaA / Bavencio® AWARE-1 breast cancer study: final biomarker data Roche / Tecentriq® Complete enrollment in BRACELET-1 metastatic breast cancer study Pfizer & Merck KGaA / Bavencio® Phase 2 BRACELET-1 metastatic breast cancer study: final data Pfizer & Merck KGaA / Bavencio® 08********08 06Dec2020 TD WaterHouse Oncolytics Biotechnology Industry Peers Industry Peers Overview Table Company sortable Market Cap sortable P/E Ratio (TTM) sortable EPS Growth (5yr) sortable Canada ONC Oncolytics Biotech Inc 221.7M Canada MDNA Medicenna Therapeutics Corp 241.7M Canada RVX Resverlogix Corp 208.2M 1.4x Canada TRP Field Trip Health Ltd 164.1M Canada TMD Titan Medical Inc 127.4M 123.0x Canada LXG Lexagene Holdings Inc 88.6M As of 2020-12-06 ********* 12Jun2020 http://www.adlainortye.com/en_product.php Hangzhou Economic & Technological Development Area, 310018, P.R.China (near Shanghai?) Adlai Nortye pelareorep breast cancer, done Phase 2, Chinese approval for Phase 3 (see below) - "Sinopep Pharmaceutical" was established in 2004. - The fund from Science and Technology Ministry in 2009. - Recognized as a “National High-tech Enterprises” in 2009. - The 11th Polypeptide Technology Application Award in 2010. - Shareholding system reform and renamed “Adlai Nortye Biopharma” in 2016. - Listed on NEEQ in Feb 21, 2017. （Stock Code：870946） - Terminated a listing on NEEQ in Mar, 2018. - Raising $53 million in Series B Round of financing in June, 2018. China Phase 3 approval : Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients. Pelareorep has received Fast Track designation and Special Protocol Assessment Agreement for phase III clinical trial from FDA for the treatment of metastatic breast cancer. And we also received approvsl from the National Medical Products Administration (NMPA) of China for initiating the open-label, randomized, multicenter, global phase III clinical trial for pelareorep (AN1004) in combination with paclitaxel in patients with advanced/ metastatic breast cancer in China. Paclitaxel - Wikipedia https://en.wikipedia.org/wiki/Paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer. It is given by injection into a vein. There is also an albumin-bound formulation.. Common side effects include hair loss, bone marrow suppression ... Bristol-Myers Squibb trade name Taxol® Pfizer & everybody else? Paclitaxel - Phyton Biotech https://phytonbiotech.com/apis/paclitaxel/ Largest Global Supplier of Paclitaxel API via PCF® Paclitaxel (sold under trade name Taxol® by Bristol-Myers Squibb) is a very effective plant-derived chemotherapy drug used to treat breast, ovarian, lung, bladder, prostate, melanoma, esophageal, as well as other types of solid tumor cancers. Japanese Oncolys https://www.oncolys.com/en/ https://www.oncolys.com/en/pipeline/ Early detection : Telomescan OBP-401/1101 into clinical usefulness stage? Local therapy : Telomelysin esophagel, gastri/gastroesophageal junction cancer Prognosis assessment: Telomescan Systemic therapy : OBP-801 Their patent page doesn't mention Oncolytics!?!?!? 03Jun2020 report https://ssl4.eir-parts.net/doc/4588/tdnet/1844266/00.pdf Oncolys BioPharma Inc.Orphan-Drug Designation of Telomelysin for Treatment of Esophageal Cancer 7-year market exclusivity ********* 11Jun2020 Royalty model of ONCY valuation : https://www.upcounsel.com/patent-licensing-royalty-rates Examples of average royalty rates by industry are as follows: Pharma and biotech, 6 percent https://www.cnbc.com/2020/01/28/pfizer-pfe-earnings-q4-2019.html Pfizer profit misses as breast cancer drug sales fall short of estimates Published Tue, Jan 28 20206:55 AM ESTUpdated Tue, Jan 28 202010:45 AM EST Sales of breast cancer drug Ibrance, a growth driver for Pfizer, rose 13% to $1.28 billion in the quarter, but missed the consensus estimate of $1.35 billion, according to IBES data from Refinitiv. Projected sales of pelareorep : Say [Pelareorep, Ibrance] sales of double current Ibrance : 3 G$ on generous side Pelareorep gets 25% of 6% royalties on combined sales (again, VERY generous for not doing any heavy [work, financing, development]!) ONCY royalty potential = 3 G$/yr * 6% royalty * 25% ONCY share = 0.0450 G$/yr or 45 M$/yr https://www.tradingview.com/symbols/NASDAQ-ONCY/ : Market Capitalization 51.003M Enterprise Value (MRQ) 30.626M Total Shares Outstanding (MRQ) 26.358M Number of Employees 23 Number of Shareholders 196 ONCY revenue/shr/yr before any further dilution : EPS guess after full market deployment, for 10 years of patent coverage? : = 45 M$/yr / (26.358 M shares) ~= 1.71 $/yr/sh >> That's not a bad guess of the current share price, considering there have never been royalty revenues that I know of? (coming up soon as time payment of Japanes Onsolys?) Very low overhead on licensing, maybe high legal costs for patent protection etc (by Pfizer - lower royalty share of Oncolytics). Use price-Earnings ratio of 40, assuming other ESTABLISHED synergistic candidates that total 3*Pfizer Ibrance. Stock Price once established market : = 40 * 3 Pfizer included royalty drug combos * 1.71 $/yr/sh = 205 $/sh stock market price, but : - ONLY after equivalent of 3 [ONCY Pelareorep, Pfizer Ibrance] equivalents [established, selling] on the market - before mature stage of drug - potential for far higher [royalties, stock price] if many new [areas, specific drugs] combos are successful - potential for ZERO royalties if patent rights not respected or circumvented (with time, good potential for the latter).