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This Quarterly Report and other publicly available documents, including any
documents incorporated herein and therein by reference, contain, and our
officers and representatives may from time to time make, “forward-looking
statements,” including within the meaning of the safe harbor provisions of the
following discussion, the words “anticipates,” “intends,” “believes,” “expects,”
“plans,”” seeks,” “estimates,” “likely,” “may,” “would,” “will,” and similar
expressions, as they relate to us or our management, are intended to identify
such forward-looking statements. Examples of forward-looking statements include,
among others, statements we make regarding (i) our plans to initiate a
randomized clinical trial; and (ii) our estimates of additional funds that may
be required to complete our development plan and obtain necessary approvals.
Forward-looking statements are neither historical facts nor assurances of future
performance. Instead, they are based only on our current beliefs, expectations
and assumptions regarding the future of our business, future plans and
strategies, projections, anticipated events and trends, the economy and other
future conditions. Because forward-looking statements relate to the future, they
are subject to inherent uncertainties, risks and changes in circumstances that
are difficult to predict and many of which are outside of our control. Our
actual results and financial condition may differ materially and adversely from
the forward-looking statements. Therefore, you should not rely on any of these
forward-looking statements. Important factors that could cause our actual
results and financial condition to differ materially from those indicated in the
forward-looking statements include, among others, the following: (i) our lack of
diversification and the corresponding risk of an investment in our Company; (ii)
potential deterioration of our financial condition and results due to failure to
diversify; (iii) our ability to successfully complete acquisitions and integrate
operations for new product candidates; (iv) our ability to obtain additional
capital, on acceptable terms or at all, required to implement our business plan;
(v) final results of our Phase I clinical trial; (vi) progress and success of
our randomized Phase II/III clinical trial; (vii) our ability to demonstrate
safety and effectiveness of our product candidate; (viii) our ability to obtain
regulatory approvals for our product candidate in
future sales of our product candidate; (x) the cost and delays in product
development that may result from changes in regulatory oversight applicable to
our product candidate; (xi) the rate of progress in establishing reimbursement
arrangements with third-party payors; (xii) the effect of competing
technological and market developments; (xiii) the costs involved in filing and
prosecuting patent applications and enforcing or defending patent claims; and
(xiv) our ability to maintain our listing on a national securities exchange
(xv) such other factors as discussed in Part I, Item 1A under the caption “Risk
Factors” in our most recent Annual Report on Form 10-K, any additional risks
presented in our Quarterly Reports on Form 10-Q and our Current Reports on Form
8-K.
Any forward-looking statement made by us in this Quarterly Report is based on
information currently available to us and speaks only as of the date on which it
is made. We undertake no obligation to publicly update any forward-looking
statement or reasons why actual results would differ from those anticipated in
any such forward-looking statement, whether written or oral, whether as a result
of new information, future developments or otherwise.
Overview
subsidiaries, “we,” “us,” “our,” and the “Company”) is a clinical stage
biopharmaceutical company developing disruptive therapeutics for the treatment
of patients with urgent unmet medical needs.
On
reorganization and acquisition of
(“CPP”) pursuant to the agreement and plan of merger, dated as of
2022
Inc.
others. Pursuant to the terms of the Merger Agreement, (i)
Subsidiary I, Inc.
which was itself a wholly-owned subsidiary of
into
First Merger, and (ii)
subsidiary of Panbela, merged with and into CPP (the “Second Merger” and,
together with the First Merger, the “Mergers”), with CPP surviving the Second
Merger. As a result of the Mergers, each of
wholly owned subsidiary of Panbela. In addition, in connection with the
consummation of the Mergers, “
Research, Inc.
Therapeutics, Inc.
Our lead candidates are ivospemin (SBP-101) for which we have exclusively
licensed the worldwide rights from the
Foundation, Inc.
delivered in an oral form. The Company has an exclusive worldwide license to
commercialize Flynpovi from the
Arizona
Ivospemin (SBP-101)
In 2015, the FDA accepted our Investigational New Drug (“IND”) application for
our ivospemin product candidate. In May of 2022 we were notified that the United
States Adopted Names (“USAN”) had adopted ivospemin as a USAN for SBP-101. The
USAN information on ivospemin was posted on the USAN Web site
(www.ama-assn.org/go/usan).
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We have completed an initial clinical trial of ivospemin in patients with
previously treated locally advanced or metastatic pancreatic cancer. This was a
Phase I, first-in-human, dose-escalation, safety study. From
through
groups, in the dose-escalation phase of the Phase I trial. No drug-related bone
marrow toxicity or peripheral neuropathy was observed at any dose level. In
addition to being evaluated for safety, 23 of the 29 patients were evaluable for
preliminary signals of efficacy prior to or at the eight-week conclusion of
their first cycle of treatment using the Response Evaluation Criteria in Solid
Tumors (“RECIST”), the currently accepted standard for evaluating change in the
size of tumors.
In 2018, we began enrolling patients in our second clinical trial, a Phase Ia/Ib
study of the safety, efficacy and pharmacokinetics of ivospemin administered in
combination with two standard-of-care chemotherapy agents, gemcitabine and
nab-paclitaxel. A total of 25 subjects were enrolled in four cohorts to evaluate
the dosage level and schedule. An additional 25 subjects were enrolled in the
expansion phase of the trial. Interim results were presented in January of 2022.
Best response in evaluable subjects (cohorts 4 and Ib N=29) was a CR in 1 (3%),
PR in 13 (45%), SD in 10 (34%) and PD in 5 (17%). One subject did not have post
baseline scans with RECIST tumor assessments. Median PFS, now final at 6.5
months, may have been negatively impacted by drug dosing interruptions to
evaluate potential toxicity. Median overall survival in Cohort 4 + Phase Ib was
12.0 months when data was presented in
months. Two patients from cohort 2 have demonstrated long term survival. One at
30.3 months (final data) and one at 33.0 months and still alive at data base
lock on
from cohort 2 and six from cohort 4 plus Ib.
In January of 2022, the Company announced the initiation of a new clinical
trial. Referred to as ASPIRE, the trial is a randomized double-blind
placebo-controlled trial in combination with gemcitabine and nab-paclitaxel, a
standard pancreatic cancer treatment regimen in patients previously untreated
for metastatic pancreatic cancer. The trial will be conducted globally at
approximately 95 sites in
company announced the first patient enrolled in the trial in
of 2022. In September, the company announced that they had obtained regulatory
approval to open sites in
45 sites open in 7 countries.
While opening of clinical sites in
has been slower than originally anticipated, due in part to resource fatigue in
the medical community, the Company expects all countries and sites to be open by
mid-2023.
The trial was originally designed as a Phase II/III with a smaller initial
sample size (150) to support the events required for interim analysis based on
progression-free survival (PFS) and a primary endpoint of overall survival. In
response to European and FDA regulatory feedback, the study was amended to
include the total trial sample size (600) and the design modified to utilize
overall survival as the primary endpoint to be examined at interim analysis. PFS
will also be analyzed to provide additional efficacy evidence. This amendment
was supported by the final data from the Phase Ia/Ib first line metastatic
pancreatic trial which completed enrollment in December of 2020. The study will
enroll 600 subjects and is anticipated to take 36 months for complete enrollment
with the interim analysis available in early 2024.
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In early
the results for ivospemin as a polyamine metabolism modulator in ovarian cancer
at the
concludes that the ivospemin chemotherapy treatment of C57Bl/6 mice injected
with VDID8+ ovarian cancer cells significantly prolonged survival and decreased
overall tumor burden. The results suggest that ivospemin in combination with
standard of care chemotherapy may have a role in the clinical management of
ovarian cancer, and the Company intends to continue pre-clinical and clinical
studies in ovarian cancer.
Additional clinical trials may be required for FDA or other country approvals.
The cost and timing of additional clinical trials are highly dependent on the
nature and size of the trials.
Flynpovi (eflornithine (CPP-1X) and sulindac)
In 2009, the FDA accepted our IND application for the combination product,
Flynpovi, product candidate.
In a Phase III study, the efficacy and safety of the combination of eflornithine
and sulindac known as Flynpovi, as compared with either drug eflornithine or
sulindac alone, in adults with familial adenomatous polyposis (“FAP”) was
conducted. A total of 171 patients underwent randomization. Disease progression
occurred in 18 of 56 patients (32%) in the Flynpovi group, 22 of 58 (38%) in the
sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard
ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for Flynpovi as
compared with sulindac (p = 0.29) and 0.66 (95% CI, 0.36 to 1.23) for Flynpovi
as compared with eflornithine. In a post-hoc analysis, none of the patients in
the Flynpovi arm progressed to a need for lower gastrointestinal (“LGI”) surgery
for up to 48 months compared with 7 (13.2%) and 8 (15.7%) patients in the
sulindac and eflornithine (CPP-1X) arms. These data corresponded to risk
reductions for the need for LGI surgery approaching 100% between Flynpovi and
either monotherapy with HR = 0.00 (95% CI, 0.00-0.48; p = 0.005) for Flynpovi
versus sulindac and HR = 0.00 (95% CI, 0.00-0.44; p = 0.003) for Flynpovi versus
eflornithine. Given the statistical significance of the LGI group, a new drug
application (“NDA”) was filed with the FDA. As the study failed to meet the
primary endpoint, and the NDA was based on the results of an exploratory
analysis, a complete response letter was issued. To address this deficiency
concern, the Company must submit the results of one or more adequate and
well-controlled clinical trials which demonstrate an effect on a clinical
endpoint.
In April of 2023 the Company regained the North American rights to develop and
commercialize Flynpovi in patients with FAP, as a result of the termination of
the licensing agreement between
We also have an ongoing double-blind placebo-controlled trial of Flynpovi to
prevent recurrence of high-risk adenomas and second primary colorectal cancers
in patients with stage 0-III colon or rectal cancer, Phase III – Preventing
Adenomas of the Colon with Eflornithine and Sulindac (“PACES”). The purpose of
this study is to assess whether the combination of eflornithine and sulindac
(compared to corresponding placebos) has efficacy against colorectal lesions
with respect to high-grade dysplasia, adenomas with villous features, adenomas
one cm or greater, multiple adenomas, any adenomas >/= 0.3 cm, total advanced
colorectal events, or total colorectal events. The PACES trial is funded by the
(“SWOG”).
Eflornithine (CPP-1X)/eflornithine sachets (CPP-1X-S)
In 2009 and 2018, the FDA accepted our IND applications for eflornithine.
There are trials evaluating eflornithine sachets in relapsed refractory
neuroblastoma supported by the
and STK11 mutation patients with non-small cell lung cancer scheduled to begin
this year. For eflornithine tablets, a Phase II trial in early onset Type I
diabetes was opened on
and the
Financial Overview
On
implementation of a reverse stock split at a ratio of one-for-forty (1:40)
shares of the Company’s common stock. The reverse stock split was effective as
of
presented have been retroactively adjusted to reflect the one-for-forty reverse
stock split.
We have incurred losses of
negative cash flows from operating activities of approximately
this period. We expect to continue to incur substantial losses, which will
generate negative net cash flows from operating activities, as we continue to
pursue research and development activities and commercialize.
Our cash was approximately
and
three months ended
activities offset in part by approximately
operations. Due to drug shortages of Abraxane, which is utilized in addition to
ivospemin for the current randomized clinical trial, the Company has explored
all avenues to procure supply and prepayments of approximately
required well in advance of delivery and is reflected in the periods cash used
in operations. Net financing activities included a registered public offering of
common stock, prefunded warrants, and warrants with net proceeds of
approximately
at-the market sales arrangement, with net proceeds of approximately
million
repayments.
We need to raise additional capital to continue our operations and execute our
business plan past the second quarter of 2023, including completing required
future trials and pursuing regulatory approvals in
our operations principally from the sale of equity securities and debt. While we
have been successful in the past in obtaining the necessary capital to support
our operations and we are likely to seek additional financing through similar
means, there is no assurance that we will be able to obtain additional financing
under commercially reasonable terms and conditions, or at all. This risk would
increase if our clinical data were not positive or if economic or market
conditions deteriorate.
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If we are unable to obtain additional financing when needed, we would need to
scale back our operations, taking actions which may include, among other things,
reducing use of outside professional service providers, reducing staff or staff
compensation, significantly modifying, or delaying the development of our
product candidates, licensing to third parties the rights to commercialize our
product candidates, or ceasing operations.
The Company has not experienced any significant disruptions to our operations as
a result of the COVID-19 pandemic. Recruitment and enrollment in our Phase Ia/Ib
trial was paused for a brief time in April and May of 2020. The drug product was
delayed during early 2022, but we had adequate supply to initiate our randomized
Phase II/III clinical trial and experienced no product related disruptions to
our clinical trials. The Company was not required to change management practices
as it was decentralized prior to the COVID-19 pandemic.
Results of Operations
Comparison of the results of operations (in thousands):
Three Months Ended March 31,
2023 2022 Percent Change
Operating Expenses
General and administrative $ 1,352 $ 1,796 -24.7 %
Research and development 3,508 2,208 58.9 %
Total operating expenses 4,860 4,004 21.4 %
Other income (expense), net (253 ) 309 -181.9 %
Income tax benefit - 29 -100.0 %
Net Loss $ (5,113 ) $ (3,666 ) 39.5 %
Research and development (“R&D”) and general and administrative (“G&A”) expenses
include non-cash share-based compensation expense resulting from our issuance of
stock options. We expense the fair value of equity awards over their vesting
periods. The terms and vesting schedules for share-based awards vary by type of
grant and the employment status of the grantee. The awards granted through
31, 2023
additional non-cash share-based compensation expense in the future, which may be
significant.
The following table summarizes the stock-based compensation expense in our
statements of comprehensive loss:
Three Months Ended March 31,
2023 2022
General and administrative $ 140 $ 271
Research and development 40 63
Total stock based compensation $ 180 $ 334
General and administrative expense
Our G&A expenses decreased 24.7% to
down from
related to reduced legal and other costs associated with the completed merger of
CPP in 2022.
Research and development expense
Our R&D expenses increased 58.9% to
up from
to increased sites and subject enrollments in the ASPIRE Randomized Phase II/III
trial in the first quarter of 2023.
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Other income (expense), net
Other expense, net, was approximately
related to foreign currency exchange loss on the intercompany receivable balance
and interest expense on two promissory notes.
Other income, net, was approximately
to foreign currency exchange gain on the intercompany receivable balance.
Liquidity and Capital Resources
The following table summarizes our liquidity and capital resources as of
31, 2023
discussion that follows (in thousands):
Liquidity and Capital Resources
March 31, 2023 December 31, 2022 Cash $ 5,235 $ 1,285 Working capital$ (1,913 ) $ (6,056 ) Cash Flow Data Three Months Ended March 31, 2023 2022 Cash Provided by (Used in): Operating Activities$ (9,751 ) $ (4,483 ) Financing Activities 13,704 - Effect of exchange rate changes on cash (3 ) 2 Net increase (decrease) in cash$ 3,950 $ (4,481 ) Working Capital
Our total cash and cash equivalents were
current liabilities and a working capital deficit of
31, 2023
deficit of
current assets less current liabilities.
Cash Flows
Net cash used in operating activities was approximately
three months ended
three months ended
primarily reflects the net loss for these periods and is partially offset by the
effects of changes in operating assets and liabilities. For the quarter ended
fund long term deposits held by the CRO leading our randomized trial. The
increase in the quarter to Net Deposits held by our CRO was offset by an
increase in Accounts Payable. Also reflected in the increased cash used in
operations is approximately
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Net Cash Provided by Financing Activities
Net cash provided by financing activities was approximately
the three months ended
activities for the three months ended
three months ended
common stock, prefunded warrants and warrants, partially offset by the payment
and payoff of promissory notes.
Capital Requirements
As we continue to pursue our operations and execute our business plan, including
the completion of the clinical development plan for our initial product
candidate, ivospemin, in pancreatic cancer, and pursuing regulatory approvals in
to continue to incur substantial and increasing losses, which will continue to
generate negative net cash flows from operating activities.
Our future capital uses and requirements depend on numerous current and future
factors. These factors include, but are not limited to, the following:
? the progress of clinical trials required to support our applications for
regulatory approvals, including the completion of our global, randomized Phase
II/III trial initiated in January of 2022;
? the cost to implement development efforts for ivospemin in ovarian cancer and
expand development efforts for assets acquired as the result of the
acquisition of CPP;
? the cost, if any, to develop our product candidate, Flynpovi;
? the cost to develop eflornithine in various indications if early clinical
trials underway now, and funded through third party collaborations, are
successful;
? our ability to demonstrate the safety and effectiveness of our product
candidates;
? our ability to obtain regulatory approval of our product candidates in the
United States , the European Union or other international markets;
? the cost and delays in product development that may result from changes in
regulatory oversight applicable to our product candidates;
? the market acceptance and level of future sales of our product candidates;
? the rate of progress in establishing reimbursement arrangements with
third-party payors;
? the effect of competing technological and market developments; and
? the costs involved in filing and prosecuting patent applications and enforcing
or defending patent claims.
As of
we could borrow funds. Historically we have financed our operations principally
from the sale of equity securities and debt. While we have been successful in
the past in obtaining the necessary capital to support our operations and we are
likely to seek additional financing through similar means, there is no assurance
that we will be able to obtain additional financing under commercially
reasonable terms and conditions, or at all.
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Indebtedness
CPP issued to
(the “Note”) on
million
Principal at a rate of 5% per annum. All unpaid Principal, together with any
then unpaid and accrued interest, is payable as follows: (i)
all interest accrued but unpaid on or before each of
31, 2024
Principal plus accrued but unpaid interest on or before
Company made the scheduled
interest. The outstanding principal balance on
approximately
Panbela has provided a Guarantee of payment in favor of the Lender for the full
amount of the Note issued to the Lender.
As of
with a former development partner,
Critical Accounting Policies and Estimates
Our significant accounting policies and estimates are set forth in the notes
accompanying the condensed consolidated financial statements included in this
document. The accounting policies and estimates used in preparing our interim
fiscal 2023 condensed consolidated financial statements are the same as those
described in our Annual Report on Form 10-K for the fiscal year ended
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