Takeda Pharmaceutical Company
Limited (“Takeda,” Osaka, Japan) and BioNumerik Pharmaceuticals, Inc.
(“BioNumerik”, San Antonio, Texas) today announced the results of two Phase
III Trials for Tavocept(TM). Tavocept is an investigational new drug with
potential for oncology and non-oncology indications that was originated and
developed by BioNumerik.

The initial development focus for Tavocept has been as an
investigational new drug to prevent or mitigate the peripheral nerve
damage, or neuropathy, that is known to be associated with certain commonly
used classes of chemotherapy drugs, such as taxane and platinum agents.
Data was recently unblinded by BioNumerik from two placebo controlled
Tavocept Phase III clinical trials consisting of (1) a Phase III trial of
weekly administration of paclitaxel (a widely used taxane drug) to patients
with metastatic breast cancer enrolled from the United States, Russia, and
Ukraine (the “Weekly Paclitaxel Breast Cancer Trial”); and (2) a Phase III
trial involving administration of paclitaxel and cisplatin (a widely used
platinum drug) every 3 weeks to patients with non-small cell lung cancer
from Eastern and Western Europe (the “European Lung Cancer Trial”). Both of
these trials were aimed at evaluating Tavocept’s potential for a neuropathy
related treatment indication.

Each of the Phase III trials was designed as a randomized double-blind
placebo controlled trial with each patient to be randomly assigned to
receive either Tavocept or placebo in conjunction with chemotherapy. The
primary endpoints for the Weekly Paclitaxel Breast Cancer Trial and the
European Lung Cancer Trial were: (1) the total incidence of severe
neuropathy caused by the administration of chemotherapy in combination with
Tavocept or placebo; and (2) the difference in rates of tumor shrinkage in
patients receiving chemotherapy in combination with Tavocept or placebo, in
order to determine whether Tavocept has an impact on the anti-tumor effect
of chemotherapy.

Based on review and analysis of the results, the trials did not meet
their primary endpoints and they were inconclusive in terms of
demonstrating a statistically significant effect of Tavocept in reducing
the incidence of severe neuropathy caused by the administration of
paclitaxel and/or cisplatin. In addition, neither of the trials
demonstrated a statistically significant finding in terms of objective
tumor response rate or tumor protection as assessed in accordance with the
predefined statistical analysis plans for the trials, or by an independent
radiological review committee.

In commenting on the data, Frederick H. Hausheer, M.D., Chairman and
Chief Executive Officer of BioNumerik stated, “Many patients suffer from
chemotherapy induced neuropathy and there is no FDA-approved treatment to
prevent or reduce neuropathy caused by taxane and platinum chemotherapy
drugs. Although we did not see the results that we hoped to observe in
these Phase III trials, we believe there is evidence of potential clinical
activity of Tavocept that supports consideration of possible further
Tavocept development aimed at addressing the large unmet medical need for
neuroprotective agents. Certain trends and subgroup analyses for the trials
indicate that Tavocept may have potential for reducing chemotherapy-induced
neuropathy that merits consideration of further clinical testing. In
addition, the way that neuropathy was measured and the countries where the
trials were conducted may also have impacted the results.”

Subgroup analysis by country from the Weekly Paclitaxel Breast Cancer
Trial revealed a notable finding in favor of Tavocept in the reduction of
patient-reported severe neuropathy (as measured by Patient Neurotoxicity
Questionnaire (PNQ) grades D or E) for patients enrolled only from U.S.
sites. In this subpopulation comprising patients enrolled only from U.S.
sites, the incidence of patient-reported severe neuropathy confirmed for at
least 4 weeks (PNQ grades D or E) was 3.2% in the Tavocept group as
compared to 20.0% in the placebo group. This observation represents an 84%
lower incidence of severe neuropathy in favor of Tavocept. The Patient
Neurotoxicity Questionnaire (or PNQ) is a patient-based neuropathy
measurement tool that was used to measure neuropathy in the Tavocept Phase
III trials. The National Cancer Institute Common Toxicity Criteria
(“NCI-CTC”), a physician-based neuropathy measurement tool, showed a
consistent trend with that of the PNQ in terms of comparing the overall
severe neuropathy reported in the Tavocept and placebo arms for patients
from U.S. sites in the Weekly Paclitaxel Breast Cancer Trial. However, it
is also important to note that only about 8% of the total number of
patients treated in the Weekly Paclitaxel Breast Cancer Trial were treated
at U.S. clinical sites.

“An important factor supporting possible future Tavocept development
for a neuropathy indication is the subgroup analysis for patients enrolled
only at clinical sites located in the United States who participated in the
Weekly Paclitaxel Breast Cancer Trial,” said Hausheer. “We also observed
some encouraging trends in the Weekly Paclitaxel Breast Cancer Trial that
indicate potential activity of Tavocept in reducing moderate to severe
neuropathy. These are some of the first Phase III trials conducted to
assess the potential reduction of chemotherapy induced neuropathy. We
believe there may be modifications in the trial endpoints in the future as
well as changes in the procedures for assessing neuropathy in order to
clinically assess patients at risk for this complication and to address
some of the technical challenges we have observed in these trials to date.
While we are encouraged by some of the observations in these trials, it is
clear that additional clinical testing will be required to support
development of Tavocept for a neuropathy indication.”

Takeda has notified BioNumerik that, given the additional time
necessary to conduct additional clinical testing for a Tavocept neuropathy
indication, one possible alternative is termination of the existing
Tavocept License and Development Alliance Agreement between Takeda and
BioNumerik for the United States and Canada. Takeda and BioNumerik are
continuing to discuss the data from the trials as well as considerations
regarding the alliance agreement and the future development of Tavocept.

About Tavocept:

Tavocept is an investigational new drug with potential for oncology and
non-oncology indications that was originated and developed by BioNumerik.
Tavocept has potential applicability in multiple therapeutic areas
including diabetic neuropathy, protection against toxicity from radiation
therapy, lymphedema and other potential medical indications. In addition to
chemotherapy induced neuropathy, BioNumerik is evaluating further Tavocept
development possibilities in these areas.

About Takeda:

Takeda, located in Osaka, Japan, is a research-based global company
with its main focus on pharmaceuticals. As the largest pharmaceutical
company in Japan and one of the global leaders of the industry, Takeda is
committed to striving toward better health for individuals and progress in
medicine by developing superior pharmaceutical products. Additional
information about Takeda is available through its corporate website,
takeda/index-e.html.

About BioNumerik:

BioNumerik, headquartered in San Antonio, Texas, is a pharmaceutical
company focused on the discovery, development and commercialization of
novel drugs for the treatment of patients with cancer. BioNumerik has two
drug candidates in late-stage clinical development: Tavocept(TM) and
Karenitecin (BNP1350).

BioNumerik Pharmaceuticals; Takeda Pharmaceutical Company
takeda/index-e.html