NTERNET
`
`ARCHIVE
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`archive.org
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`AFFIDAVIT OF NATHANIEL E FRANK-WHITE
`
`1.
`
`I ama Records Request Processor at the Internet Archive. I make this declaration
`of my ownpersonal knowledge.
`
`2. The Internet Archive is a website that provides access to a digital library of Internet
`sites and other cultural artifacts in digital form. Like a paper library, we provide
`free access to researchers, historians, scholars, and the general public. The Internet
`Archive has partnered with and receives support from variousinstitutions,
`including the Library of Congress.
`
`3. The Internet Archive has created a service known as the Wayback Machine. The
`Wayback Machine makesit possible to browse more than 450 billion pages stored
`in the Internet Archive's web archive. Visitors to the Wayback Machine can search
`archives by URL (i.e., a website address). If archived records for a URL are
`available, the visitor will be presented with a display of available dates. The visitor
`may select one of those dates, and begin browsing an archived version of the Web.
`Links on archivedfiles in the Wayback Machine pointto other archived files
`(whether HTMLpagesor otherfile types), if any are found for the URL indicated
`by a given link. For instance, the Wayback Machineis designed such that when a
`visitor clicks on a hyperlink on an archived page that points to another URL,the
`visitor will be served the archivedfile found for the hyperlink’s URL with the
`closest available date to the initial file containing the hyperlink.
`
`4. The archived data made viewable and browsable by the Wayback Machineis
`obtained by use of web archiving software that automatically stores copies offiles
`available via the Internet, each file preservedas it existed at a particular pointin
`time.
`
`5. The Internet Archive assigns a URL onits site to the archivedfiles in the format
`http://web.archive.org/web/[Year in yyyy][Month in mm][Dayin dd][Time code in
`hh:mm:ss]/[Archived URL] aka an “extended URL”. Thus, the extended URL
`http://web.archive.org/web/19970126045828/http://www.archive.org/ would be the
`URLfor the record of the Internet Archive home page HTMLfile
`(http://www.archive.org/) archived on January 26, 1997 at 4:58 a.m. and 28
`seconds (1997/01/26 at 04:58:28). The date indicated by an extended URL applies
`to a preserved instanceofafile for a given URL,but not necessarily to any other
`files linked therein. Thus, in the case of a page constituted by a primary HTMLfile
`and other separate files (e.g., files with images, audio, multimedia, design
`elements, or other embedded content) linked within that primary HTMLfile, the
`primary HTML file and the other files will each have their own respective extended
`URLsand maynot have been archived on the samedates.
`
`6. Attached hereto as Exhibit B are true and accurate copies of the Internet Archive's
`records of the archivedfiles for the URLs andthe dates specified in the attached
`coversheet ofeach file.
`
`OnNOReNeneTIEDSBCF-SS795898A4CD 1A
`Apotex v. Cellgene - IPR2023-00512
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`FEF ARCHIVE
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`pe
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`w— a
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`Dh
`archive.org
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`7.
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`Ideclare under penalty of perjury that the foregoing is true and correct.
`
`DATE:_02/06/2023 Nathaniel Frank-White
`
`Nathaniel E Frank-White
`
`
`
`Please see attached
`All Purpose
`Jurat form
`for additional
`Notary Events
`
`OnlineNotary.net
`Coaument it: BB076060-AG67-11ED-BBCF-ES785B96A40D
`
`LLLA
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`EXHIBIT B
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`t Id: B6O76060-A667-11ED-8BCF-53795B96A4CD
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`OnlineNotarynet
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`Apotex v. Cellgene - IPR2023-00512
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`Apotex v. Cellgene - IPR2023-00512
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`https://web.archive.org/web/20071013020700/http:/www.mds-foundation.org/pdf/oral-aza.pdf
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`OnlneNGtaEnnoSa7asBOBAACD
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`FINAL - for release at 7am Eastern on Wednesday, August 29
`
`Pharmion’s Oral Azacitidine Granted Fast Track Status for
`Myelodysplastic Syndromes
`
`BOULDER,Colo., August 29, 2007 — Pharmion Corporation (NASDAQ: PHRM)
`today announcedthat the U.S. Food and Drug Administration (FDA) has granted Fast
`Track designation for oral Azacitidine in the treatment of Myelodysplastic Syndromes
`(MDS).
`
`Fast Track programs are designed to facilitate the development and expedite the review
`of new drugs that are intended to treat seriousorlife-threatening conditions and that
`demonstrate the potential to address unmet medical needs. Fast Track emphasizes the
`critical nature of close, early communication between the FDA and sponsors. The
`benefits of Fast Track include scheduled meetings to seek FDAinput into development
`plans, and the option of submitting a New Drug Application in sections rather than all
`components simultaneously. These meetings can help the FDA and sponsors reach
`early agreement on design ofthe clinical efficacy studies that will be needed to support
`approval.
`
`The FDAstated that Fast Track designation was granted for oral Azacitidine for MDS
`because Azacitidine is approvedto treat all subtypes of MDS, and becauseit will
`potentially provide a safer, more comfortable, more convenient and moreefficient route
`of administration of Azacitidine.
`
`“We are extremely enthusiastic about working closely with Pharmionto drive the
`developmentof oral Azacitidine,” said Dr. Hagop Kantarjian, chair of the department of
`leukemia at the University of Texas M.D. Anderson Cancer Center. “Vidaza has now
`demonstrated a unique and profound survival benefit in higher-risk MDS, and wethink
`oral Azacitidine may provide significant benefit in treating lower risk forms of MDS as
`well. We are delighted that the FDA shares our view that its development should be
`expedited. The opportunity to explore the biological and clinical consequencesof
`continuous oral dosing of Azacitidine is particularly exciting, since we know that DNA
`remethylation occurs betweencycles of intermittent parenteral therapy. Effects of
`continuous Azacitidine dosing on tumor RNA,another potential azacitidine target, will
`also be exploredforthefirst time.”
`
`Pharmion currently markets the parenteral formulation of azacitidine, known as Vidaza®
`(azacitidine for injection) for the treatment of patients with Myelodysplastic Syndromes
`(MDS).
`In January 2007 the FDA approved a new drug application supplement to add
`intravenous use as a new route of administration to instructions in the prescribing
`information for Vidaza. Earlier this month, Pharmion announcedtopline results from the
`largest study ever conductedin higher-risk MDS, which demonstrated a significant
`improvementin survival for patients treated with Vidaza.
`In the primary endpoint
`analysis, Vidaza treatment was associated with a median survival of 24.4 months versus
`15 monthsfor those receiving conventional care regimens, an improvementof 9.4
`months (p<0.0001).
`
`Pharmionis exploring oral Azacitidine’s utility in the treatment of MDS and other cancers
`where demethylation may provide an anti-tumor effect. Oral Azacitidine is the subject of
`
`PHRMOralAzafast track status FINAL 8 29 2007.doc
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`a Phase 1 multi-center, open label dose escalationtrial that will assess the maximum
`tolerated dose, doselimiting toxicities and safety of a seven day, multi-cycle oral dosing
`regimenof oral Azacitidine in patients with MDS and AML.
`In addition, thetrial will
`examine pharmacokinetics and pharmacodynamiceffects of orally administered
`Azacitidine, as compared with parenteral Vidaza.
`
`An oral dosage formulation of Azacitidine, in addition to the more desirable and
`convenient route of administration, would enable the evaluation of a low-dose regimen
`that could maximize demethylation and gene re-expression, as well as the evaluation of
`long-term or maintenancetherapy.
`
`Contact details
`
`Breanna Burkart or Anna Sussman
`Directors, Investor Relations and Corporate Communications
`Pharmion Corporation
`Tel: +1 720 564 9144 or +1 720 564 9143
`
`About Vidaza
`
`Vidaza wasthefirst drug approvedfor the treatmentof all five subtypes of
`myelodysplastic syndromes (MDS), including refractory anemia (RA), refractory anemia
`with ringed sideroblasts (RARS)(if accompanied by neutropenia or thrombocytopenia or
`requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia
`with excessblasts in transformation (RAEB-T), and chronic myelomonocytic leukemia
`(CMMoL).
`
`Vidazais believed to exert its antineoplastic effects by causing hypomethylation of DNA
`and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The
`concentration of azacitidine required for maximum inhibition of DNA methylation in vitro
`does not cause major suppression of DNA synthesis. Hypomethylation may restore
`normalfunction to genesthat arecritical for differentiation and proliferation. The
`cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer
`cells that are no longer responsive to normal growth control mechanisms. Non-
`proliferating cells are relatively insensitive to Vidaza.
`
`Important Safety Information
`
`Vidazais contraindicated in patients with a known hypersensitivity to azacitidine or
`mannitol and in patients with advanced malignant hepatic tumors.In clinical studies, the
`most commonly occurring adverse reactions were nausea (70.5%),
`anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%),
`leukopenia (48.2%), diarrhea (36.4%), fatigue (35.9%), injection site erythema (35.0%),
`constipation (33.6%), neutropenia (32.3%) and ecchymosis (30.5%). Other adverse
`reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia(16.4%),
`myalgia (15.9%), injection site reaction (13.6%), aggravated fatigue (12.7%) and malaise
`(10.9%). Because treatment with Vidaza is associated with neutropenia and
`thrombocytopenia, complete blood counts should be performed as needed to monitor
`response and toxicity, but at a minimum, prior to each dosing cycle. Because azacitidine
`is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution
`is needed in patients with liver disease. In addition, azacitidine and its metabolites are
`
`PHRMOralAzafast track status FINAL 8 29 2007.doc
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`substantially excreted by the kidneys and therisk of toxic reactions to this drug may be
`greaterin patients with impaired renal function. Because elderly patients are morelikely
`to have decreased renal function, it may be useful to monitor renal function. Vidaza may
`cause fetal harm. While receiving treatment with Vidaza, women of childbearing potential
`should avoid becoming pregnant, and men should avoid fathering a child. In addition,
`womentreated with Vidaza should not nurse.
`
`About MDS
`
`The highest prevalence of MDSis in patients over 60 years of age. According to the
`American Cancer Society and the Aplastic Anemia and MDSInternational Foundation,
`there are approximately 10,000-30,000 new cases of MDSin the United States each
`year. Survival ranges from six months to manyyearsfor the different subtypes of MDS.
`
`About Epigenetics
`
`DNA methylation and histone deacetylation are two of the more studied epigenetic
`regulators of gene expression. Epigenetics refers to changesin the regulation of gene
`expression. Epigenetic changes can silence gene expression and, unlike DNA
`mutations, may be reversedby targeting the enzymesinvolved. Thesilencing of key cell
`cycle control genes and tumor suppressor genes through these two mechanismsof
`epigenetic regulation have been demonstratedin vitro and in vivo in hematological
`malignancies and in solid tumors. Vidaza has been shownto reverse the effects of DNA
`hypermethylation with subsequent gene re-expression and likewise MGCDO0103 has
`been shown, in vivo, to reverse the effects of inappropriate deacetylation resulting in
`gene expression reactivation. The epigenetic approach to cancertherapyis that rather
`than using molecules that kill both normal and tumorcells, the silenced genes are
`reactivated through targeted epigenetic therapy, re-establishing the cancercell's natural
`mechanismsto control abnormal growth.
`
`About Pharmion
`
`Pharmionis a leading global oncology company focused on acquiring, developing and
`commercializing innovative products for the treatment of hematology and oncology
`patients in the U.S., Europe and additional international markets. Pharmion has a
`numberof products on the marketincluding the world's first approved epigenetic drug,
`Vidaza®, a DNA demethylating agent. For additional information about Pharmion, please
`visit the company's website at www.pharmion.com.
`
`Safe Harbor Statement underthe Private Securities Litigation Reform Actof 1995: This
`release contains forward-looking statements, which express the current beliefs and expectations of
`management, including statements related to the potential efficacy of oral Azacitidine and Vidaza. Such
`statements are based on current expectations andbeliefs only and are subjectto risks and uncertainties,
`many of which are beyond our control, which could cause the actual results to differ significantly from the
`results expressed or implied by such statements. Actual results could differ materially depending on a
`numberoffactors, and we caution investors not to place undue reliance on the forward-looking statements
`containedin this press release. Important factors that could cause or contribute to such differences include,
`but are notlimited to, the potential failure of product candidates, including oral Azacitidine, to demonstrate
`safety andefficacyin clinical and non-clinical testing; the possibility that topline results from theclinicaltrial
`discussedin this press release will not be confirmed uponfull analysis of the results of the trial and that
`additional information relating to the safety, efficacy or tolerability of Vidaza may be discovered upon further
`analysis of data from thattrail or analysis of data from other ongoing Vidazaclinicaltrials; the ability to
`
`PHRMOralAzafast track status FINAL 8 29 2007.doc
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`Apotex v. Cellgene - IPR2023-00512
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`complete regulatory submissions and gain regulatory approvals in a timely manner; the ability to initiate and
`completetrials at the referenced times; the impact of competition from other products under development by
`Pharmion's competitors; the uncertainty of the regulatory environment and changesin the health policies of
`various countries; uncertainties regarding market acceptance of products newly launched, currently being
`sold or in development; andthefailure of third-party manufacturers to produce the product volumes required
`on a timely basis. Additional risks and uncertainties relating to Pharmion andits business can be foundin
`the "Risk Factors" section of Pharmion’s Quarterly Report on Form 10-Q for the quarterly period ended June
`30, 2007, its Annual Report on Form 10-K for the year ended December31, 2006 andin ourotherfilings
`with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date
`on which they are made, and Pharmion undertakesno obligation to update publicly or revise any forward-
`looking statement, whetheras a result of new information, future developments or otherwise.
`
`HHH
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`JURAT ATTACHMENT
`
`A notary public or other officer completing this certificate verifies only the identity of the individual who signed
`the document to which this certificate is attached, and not the truthfulness, accuracy, or validity of that
`document.
`
`STATEOF_Tennessee
`
`COUNTY OF
`
`Cheatham
`
`
`
`
`The foregoing instrument was subscribed and sworn before methis date of
`_02/06/2023_,by _Nathaniel Frank-White
`
`This notarial act was an online notarization.
`
`». SAMANTHA B. DOMINGUEZ
`&\
`STATE OF TENNESSEE
`E}
`NOTARY PUBLIC
`7 COUNTY OF CHEATHAM
`
`ONLINE NOTARY PUBLIC
`MY COMMISION EXPIRES: JULY 26 2025
`
`(Notary Seal)
`
`Notary’s Signature
`
`& rth B: ps
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`Registration No.: 0
`
`Commission Expiration Date:
`
`July 26, 2025
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`OnlnONStanyTIED-SBCF-S8795896A4CD
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