8-K

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                       ----------------------------------

                                    FORM 8-K

                                 CURRENT REPORT

                       PURSUANT TO SECTION 13 OR 15(d) OF
                       THE SECURITIES EXCHANGE ACT OF 1934

Date of Report (Date of earliest event reported)   November 7, 2000
                                                  ------------------------------

                           ONYX PHARMACEUTICALS, INC.
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             (Exact name of registrant as specified in its charter)


          Delaware                   0-28298                  94-3154463
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(State or other jurisdiction       (Commission              (IRS Employer
     of incorporation)             File Number)           Identification No.)


              3031 Research Drive, Richmond, California   94806
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               (Address of principal executive offices) (Zip Code)


       Registrant's telephone number, including area code (510) 222-9700
                                                          ----------------------

                                 NOT APPLICABLE
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          (Former name or former address, if changed since last report)



ITEM 9.  Regulation FD Disclosure

     Pursuant to Regulation FD, information is being furnished below with
respect to presentations made by scientists and clinical investigators of
Onyx Pharmaceuticals, Inc. ("Onyx"), on November 7, 2000. Attached and
incorporated herein by reference are abstracts of these presentations given
at the EORTC/NCI/AACR, November 7, 2000 Conference. These abstracts are being
furnished under Item 9, as Exhibits 99.1, 99.2, 99.3, and 99.4, attached
hereto.




                                   SIGNATURES

     Pursuant to the requirements of the Securities Exchange Act of 1934, as
amended, the registrant has duly caused this report to be signed on its behalf
by the undersigned hereunto duly authorized.

                                   ONYX PHARMACEUTICALS, INC.


Date: January 16, 2001             By: /s/ Gregory Giotta
                                       -----------------------------------
                                   Name: Gregory Giotta, Ph.D., J.D.
                                   Title: Vice President and Chief Legal Counsel




                                  EXHIBIT INDEX

Exhibit
Number   Description of Document
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99.1     Abstract, Introduction and Summary

         Johnson et al., "Adenovirus targeting deregulation of the RB tumor
         suppressor pathway in cancer cells demonstrate potent anti-tumor
         activity."

99.2     Abstract, Introduction, Strategy and Conclusion

         Laquerre et al., "p53-selectively replicating adenoviruses expressing
         the cytosine deaminase prodrug converting enzyme."

99.3     Abstract and Study Summary

         Reid et al., "Intra-arterial administration of a replication-selective
         adenovirus CI-1042 (ONYX-015) in patients with colorectal carcinoma
         metastatic to the liver: safety, feasibility and biological activity."

99.4     Abstract, Summary and Conclusion

         Shen et al., "Analyses of single amino acid substitution mutants of
         adenovirus type 5 E1B-55K protein."

EX-99.1

                                                                    EXHIBIT 99.1

                                    Abstract

Adenovirus targeting deregulation of the RB tumor suppressor pathway in cancer
cells demonstrate potent anti-tumor activity.

L. Johnson, A. Sampson-Johannes, S. McCoy, J. Holt, T. Hermiston and A. Fattaey.

Onyx Pharmaceuticals, Inc., Richmond, CA 94806

We have developed human adenoviruses that selectively replicate based upon
deregulation of the pRb-signaling pathway in human cancers. Disruption of
this signaling cascade has been linked to a variety of different tumor types
and can occur through genetic alteration of a number of different components
that lie within this pathway (e.g., p16, cdk4, cyclin D and pRb). Through its
binding to cellular transcription factors such as E2F, pRb and its associated
proteins can function as a transcriptional repressor complex that regulates
cell cycle progression regardless of the tissue of origin of the infected
cells. For human adenoviruses, one function of their E1A proteins is to
sequester pRb and its related family members, thereby rendering the cell
permissive to both viral and cellular DNA synthesis. The human adenovirus,
ONYX-838, encodes a mutant E1A gene whose products are no longer capable of
binding to and inactivating pRb. We have further engineered ONYX-838 to
create a series of viruses whose early gene expression patterns are dependent
upon abnormal E2F activity as a result of deregulated pRb pathway signaling.
These viruses have demonstrated anti-tumor activity similar to wildtype human
adenovirus both IN VITRO and IN VIVO. The E2F-dependent regulation engineered
into these viruses has significantly reduced the expression of certain early
genes in normal human primary cells, regardless of their proliferative state,
and underscores the tumor cell selectively built into these viruses. This
marked decrease in early gene expression translates into reduced late gene
expression and an attenuated viral infection. The very limited toxicity that
is associated with these viruses in normal, human primary cells IN VITRO is
also observed IN VIVO and may have important safety implications following
systemic administration. This strategy to combine alterations in E1A with
E2F-dependent regulation of early viral gene expression has yielded
therapeutic viruses that are both safe and highly selective for the loss of
an intact pRb pathway in human cancers.

                                  Introduction

We have exploited the use of selectively replicating viral therapy to engineer
and develop human adenoviruses that will replicate based upon deregulation of
the pRb-signaling pathway in human cancers. Disruption of this signaling cascade
has been linked to a variety of different tumor types and can occur through
genetic alteration of a number of different components that lie within this
pathway (e.g., p15, cdk4, cyclin D and pRb). Through its binding to cellular
transcription factors such as E2F, pRb and its associated proteins can function
as a transcriptional repressor complex that regulates the expression of
E2F-responsive genes and, hence, cell cycle progression regardless of the tissue
of origin of the infected cells. For human





adenoviruses, one function of their E1A proteins is to sequester pRb and its
related family members, thereby rendering the cell permissive to both viral
and cellular DNA synthesis. The human adenovirus, DL922/47 (ONYX-838),
encodes a mutant E1A gene whose products are no longer capable of binding to
an inactivating pRb. We have engineered further ONYX-838 to create a series
of viruses whose early gene expression patterns are dependent upon abnormal
E2F activity as a result of deregulated signaling within the pRb pathway.
These viruses have demonstrated anti-tumor activity similar to wild-type
human adenovirus both IN VITRO and IN VIVO. The E2F-dependent regulation
engineered into these viruses has significantly reduced the expression of
certain early genes in normal human primary cells, regardless of their
proliferative state, and underscores the tumor cell selectivity built into
these viruses. This marked decrease in early gene expression translates into
drastically reduced late gene expression and an attenuated viral infection.
The very limited toxicity that is associated with these viruses in normal,
human primary cells IN VITRO is also observed IN VIVO and may have important
safety implications following systemic administration. This strategy to
combine alterations in E1A and E2F-dependent regulation of early viral gene
expression has yielded therapeutic viruses that we believe are both safe and
selective for the loss of an intact pRb-pathway in human cancers.


                                     Summary

The enhanced selectivity of the E1A and E2F-dependent viruses results in a
substantially increased therapeutic index in animal models of human cancer.

The RB-targeted Adenoviruses demonstrate efficacy that:

The RB-targeted Adenoviruses demonstrate activity that is responsive to the
functional status of pRb.

The RB-targeted Adenoviruses demonstrate enhanced safety, both IN VIVO and IN
VITRO, compared to wild-type Adenovirus, with restricted expression/activity
regardless of their proliferative status.

Onyx currently plans to file an IND by the end of 2001 to test the
RB-targeted viruses in a human clinical trial for the treatment of cancer.




FORWARD-LOOKING STATEMENT

This abstract contains certain forward-looking statements regarding the
development of potential human therapeutic products that involve a number of
risks and uncertainties. Actual events may differ from Onyx's expectations.

EX-99.2

                                                                    EXHIBIT 99.2

                                    Abstract

P53-selectively replicating adenoviruses expressing the cytosine deaminase
prodrug converting enzyme

S. Laquerre, M.D. Young, L. Johnson, J. Nye, L. Hawkins, S. Weber, P. Holman, M.
Lemmon, S. McCoy, L. Cohen, W. Collard and T. Hermiston

Onyx Pharmaceuticals, Inc, Richmond, CA 94806

Cancer is a major cause of death in the United States and new approaches are
clearly needed to prevent and/or treat the disease. Gene transfer of
chemosensitization genes is a promising cancer therapy strategy, with the
potential for higher active drug concentrations within tumors while
minimizing systemic toxicity. To take advantage of the prodrug converting
enzyme strategy, we modified a selectively replicating adenovirus CI-1042
(ONYX-015) to encode the E. COLI cytosine deaminase (CD) gene. The CD gene
was placed in multiple, distinct loci within the virus and expressed using
endogenous, viral promoters. Analysis of these viruses demonstrated that i)
the CD prodrug converting enzyme was expressed in infected cells and was
capable of converting 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), ii)
the IN VITRO oncolytic effect of the virus expressing CD is increased in the
presence of 5-FC, and iii) the levels of 5-FU achieved after conversion of
5-FC within the tumor were higher than those reported to have a
chemotherapeutic effect. In contrast the plasma levels of 5-FU were much
lower than the tumor levels, implying reduced systemic toxicity.

                                  Introduction

CANCER:

Although an increasing number of genes are found to be altered in human cancers,
mutations in components of the Ras signal transduction pathway, the RB and p53
tumor suppressor pathway, and the activation of telomerase are common features
of nearly all human cancers.

CI-1042 (ONYX-015) MECHANISM OF ACTION:

At Onyx Pharmaceuticals, we have pioneered the use of selectively replicating
adenoviruses as new therapeutic agents for the treatment of human cancer. The
first of these viruses, CI-1042 (ONYX-015), is a human adenovirus that has
been genetically engineered to lack the E1B55K gene, the product of which
binds to cellular p53 protein. In concert with another adenovirus encoded
protein, E4ORF6, E1B55K functions to target p53 for degradation in infected
cells. CI-1042 (ONYX-015) is therefore incapable of inactivating p53
function. Infection of normal human cells with CI-1042 (ONYX-015) results in
an upregulation of p53 protein and an attenuation of the virus' ability to
produce new viral progeny. Infection of human cancer cells with CI-1042
(ONYX-015) results in the unchecked continuation of the virus replication
cycle, the cancer cells are killed, new virus progeny are produced, and
neighboring cancer cells are infected to start the virus life cycle anew. To
date,



CI-1042 (ONYX-015) has been studied in Phase II clinical trials in head and
neck cancer patients; in Phase I/II trials in patients with colorectal cancer
and with metastases to the liver and pancreatic cancer patients; and in Phase
I studies in patients with ovarian and lung cancers.

PRODRUG CONVERTING ENZYMES:

Although the results of these clinical trials are very encouraging, we have
developed a system permitting insertion of therapeutic transgenes into the
virus genome in order to expand the range of cancer indications served by our
selectively replicating viruses including gp19K, ADP and E3b. This approach
takes advantage of the endogenous viral promoters and the virus replication
cycle to express the transgenes, thereby coupling transgene expression to
virus replication. The significant features of this technology are selective
expression and amplification of the transgenes within the local tumor
environment. A number of anti-cancer chemotherapeutic agents are prodrugs.
Prodrugs are the inactive form of a drug that requires specific enzymatic
modifications to be converted to their active form. The E. COLI cytosine
deaminase gene, CD, is one such enzyme and it is capable of converting
5-fluorocytosine (5-FC), an antifungal agent into 5-flurouracil (5-FU), an
anti-cancer chemotherapeutic agent commonly used for the treatment of head
and neck and colorectal cancers.

                                    Strategy

Our strategy has been to insert and express the E. coli CD gene from the
p53-selective replicating virus' genome. We envision a development strategy
whereby the CD-armed selectively replicating virus is administered to patients
and in the presence of the prodrug 5-FC, the CD-armed virus would not only
reproduce itself, but also result in the expression of high levels of CD
transcripts. Because the virus replicates selectively in the cancer tissue, in
the presence of administered 5-FC, it should also steadily increase the
concentration of 5-FU in the cancer mass. This should expose the cancer cells to
higher levels of 5-FU than is possible with systemic administration of 5-FU.
Replication and production of new virus progeny should also result in higher
levels of transduction and transgene expression than is possible via any other
mode of gene delivery. Selective expression of CD and conversion of 5-FC to 5-FU
at the tumor site should also minimize systemic exposure and toxicity.

                                   Conclusion

1)       5-FC was detected in tumor and plasma of CI-1042 (ONYX-015) injected
         animals, and as expected no 5-FU was detected.

2)       In ONYX-700 injected tumor as well as in their plasma, the level of
         5-FC was similar to that detected in CI-1042 (ONYX-015) treated
         animal, however a small conversion was observed at 2 h post 5-FC
         injection.

3)       The level of 5-FC detected in tumor of animal treated with ONYX-740 was
         lower than that detected in tumor of animal treated with CI-1042
         (ONYX-015) or ONYX-700, presumably due to the high level of 5-FC to
         5-FU conversion in these tumors. The level of 5-FC in plasma of animal
         treated with ONYX-740





         was similar than that of animal treated with CI-1042 (ONYX-015) and
         ONYX-700 and little 5-FU was detected in the plasma of ONYX-740
         treated animal.

Thus, by incorporating a gene encoding a pro-drug converting enzyme into a
selectively replicating adenovirus, we have increased the potency of this
replicating virus, as determined by both in vitro and in vivo assays. This
"Armed Therapeutic Virus-TM-" is expected to have a higher therapeutic index
when used to treat human cancer.




FORWARD-LOOKING STATEMENT

This abstract contains certain forward-looking statements regarding the
development of potential human therapeutic products that involve a number of
risks and uncertainties. Actual events may differ from Onyx's expectations.

EX-99.3

                                                                    EXHIBIT 99.3

                                    Abstract

Intra-arterial administration of a replication-selective adenovirus Cl-1042
(ONYX-015) in patients with colorectal carcinoma metastatic to the liver:
safety, feasibility and biological activity

T. Reid, E. Galanis, J. Abbruzzese, D. Sze, J. Andrews, B. Radlev, L. Romel, J.
Rubin and D. Kirn

Both replication-incompetent and replication-selective adenoviruses are being
developed for the treatment of cancer and other diseases. A phase I/ II dose
escalation trial was performed in patients with liver-predominant
gastrointestinal carcinoma (n=33 total; primarily colorectal). Inclusion
criteria included KPS > 70%, AST/ALT < 3 times the upper limit of normal,
T.bili < 2.0, and < 50% liver replacement by tumor. CI-1042 (ONYX-015) was
infused into the hepatic artery at doses of 2x10(8) - 2x10(12) particles for
two cycles (days 1 and 8). Subsequent cycles of CI-1042 (ONYX-015) were
administered in combination with intravenous 5-fluorouracil (5-FU) and
leucovorin. No dose-limiting toxicity, maximally-tolerated dose or
treatment-emergent clinical hepatotoxicity were identified following CI-1042
(ONYX-015) infusion. Mild to moderate fever, rigors and fatigue were the most
common adverse events. Expression of IL-1, -6, tumor necrosis factor and
interferon-gamma increased within 3 hours and IL-10 by 18 hours. Antibody
titers increased significantly in all patients. Objective responses were
demonstrated in combination with chemotherapy, including one patient who was
refractory to both 5-FU and CI-1042 (ONYX-015) as single agents. Viremia was
observed 3 days after infusion in patients treated at the highest dose
levels. Of the 33 patients enrolled in the study, the survival of the 27
patients receiving the highest doses of CI-1042 (ONYX-015) is prolonged
compared to the survival of the 6 patients treated during the dose escalation
phase. Hepatic artery infusion of the attenuated adenovirus CI-1042
(ONYX-015) was well-tolerated, there were no dose limiting toxicities and
there was evidence of infection, replication and antitumoral activity.

                                  Study Summary

SAFETY. In this phase I/II study, CI-1042 (ONYX-015) was administered by hepatic
artery infusion into patients with measurable gastrointestinal cancer involving
the liver. Treatment was initiated at 10e7 pfu/infusion and escalated in 0.5 log
increments to 10e11 pfu/infusion. There have been no dose-limiting toxicities;
however, most patients experienced grade I/II fevers. Transient rigors starting
1 to 2 hours after the infusion were common in the patients treated at the
highest dose levels and were readily controlled with Benadryl or Demerol and
Phenergan. Other adverse reactions included anemia, cytopenias, nausea,
mucositis and fatigue.

RESPONSE/SURVIVAL. 33 patients were enrolled in the study. 6 patients were
treated in the dose escalation phase and 27 patients were treated at the
highest administered dose. The survival of the patients who received the
highest doses of



CI-1042 (ONYX-015) is prolonged compared to the patients on the dose escalation
phase of the study.

VIRAL REPLICATION. The virus is rapidly cleared from the blood following
arterial infusion, but the second peak of activity observed 3 days following the
infusion suggests ongoing viral replication.

CYTOKINE ANALYSIS. IL-1, IL-6, TNF, and IFN gamma increased significantly by 3
hours following infusion, especially IL-1 which was undetectable at baseline.
The expression of these cytokines returned to near baseline by 18 hours after
infusion. In contrast, IL-10 expression remained unchanged at 3 hours following
infusion of CI-1042 (ONYX-015), but was increased by 18 hours following the
infusion. Baseline levels of interferon, TNF, IL-6 and IL-10 are elevated in
subsequent cycles (cycles 2-4) following exposure to CI-1042 (ONYX-015).

SELECTIVITY. Despite the extensive tumor necrosis observed in these patients,
treatment resulted in only minor and transient increases in serum transaminase
levels, confirming the safety and selectivity of CI-1042 (ONYX-015) administered
by hepatic artery infusion.




FORWARD-LOOKING STATEMENT

This abstract contains certain forward-looking statements regarding the
development of potential human therapeutic products that involve a number of
risks and uncertainties. Actual events may differ from Onyx's expectations.

EX-99.4

                                                                    EXHIBIT 99.4

                                    Abstract

Analyses of single amino acid substitution mutants of adenovirus type 5 E1B-55K
protein

Y. Shen, G. Kitzes, J. Nye, A. Fattaey and T. Hermiston

The E1B-55K protein plays an important role during the human adenovirus type
5 (Ad5) productive infection. E1B-55K binds specifically to the p53 tumor
suppressor protein, blocking p53-mediated transcription activation. In
addition, E1B-55K collaborates with another adenovirus protein, E4orf6, to
target p53 for active degradation in the cytoplasm. During the late phase of
the viral infection, a protein complex that includes E1B-55K and E4orf6
modulates mRNA trafficking, facilitating efficient nuclear export of late
viral mRNAs while inhibiting the nucleocytoplasmic transport of cellular
mRNAs. In CI-1042 (ONYX-015), the E1B-55K gene is deleted, attenuating the
viral infection in normal cells and restricting the productive infection to
tumor cells lacking p53 function. Restoring the late functions of the E1B-55K
protein to the exclusion of p53 interaction may enhance the replication
efficiency and the anti-cancer efficacy. In an effort to separate the p53
binding/inactivation function and the late functions of the E1B-55K protein,
we have generated 26 single amino acid mutations in the E1B-55K protein.
These mutants were characterized for their ability to modulate p53 level,
interact with the E4orf6 protein, mediate viral late gene expression, and
support virus replication in human cancer cells.

                                     Summary

The E1B-55K protein plays an important role both during the early phase and
the late phase of the human adenovirus type 5 (Ad5) productive infection. In
CI-1042 (ONYX-015), the E1B-55K gene is deleted, attenuating the viral
infection in normal cells and restricting the productive infection to tumor
cells lacking p53 function. In this study, we have generated twenty-six
single amino acid mutations in the E1B-55K protein and characterized their
ability to modulate p53 level, interact with the E4orf6 protein, mediate
viral late gene expression, and support virus replication in human cancer
cells. Two mutants appeared to have lost their ability to inactivate p53 but
have retained, at least partially, the late functions of the wild-type
protein. The ability to separate the p53-inactivation activity and the late
functions of E1B-55K raises the possibility to generate adenovirus variants
that retain the tumor selectivity of CI-1042 (ONYX-015), but can replicate
more efficiently than CI-1042 (ONYX-015) in a wide spectrum of cell types. We
believe this study may provide insights for new therapeutic viruses with
increased efficacy for the treatment of human cancers.

                                   Conclusion

In this study, we have constructed a series of single amino acid substitution
mutations in the p53-binding domain and the transcriptional repression domain of
the E1B-55K protein. These mutations were recombined into an infectious virus





(dl309) background and characterized for their abilities to modulate p53
level, interact with the E4orf6 protein, mediate viral late functions, and
support virus replication in human cancer cells. Two E1B-55K mutants, R240A
and H260A, appeared to have lost the ability to inactivate p53 but have
retained, at least partially, the late functions of the wild-type protein.
R240A fully restored the wild-type replication capacity of CI-1042 (ONYX-015)
in human cancer cells, while H260A did so only partially. The ability to
separate the p53-inactivation activity and the late functions of E1B-55K
raises the possibility to generate adenovirus variants that retain the tumor
selectivity of CI-1042 (ONYX-015), but can replicate more efficiently than
CI-1042 (ONYX-015) in a wide spectrum of cell types.




FORWARD-LOOKING STATEMENT

This abstract contains certain forward-looking statements regarding the
development of potential human therapeutic products that involve a number of
risks and uncertainties. Actual events may differ from Onyx's expectations.