NOX-A12 combination trials advancing well
and balance sheet strengthened
Regulatory News:
NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a
biotechnology company focused on improving cancer treatments by
targeting the tumor microenvironment (TME), released today its
interim 2020 results for the six months ended June 30, 2020.
“Despite the challenging operational environment posed by
COVID-19, the NOXXON team, along with dedicated clinical
researchers, was able to finalize the NOX-A12 plus immunotherapy
trial in pre-treated microsatellite stable metastatic pancreatic
and colorectal cancer patients. The final trial results including
overall survival and the safety profile warrant further clinical
development of NOX-A12 plus immunotherapy combinations. We also
advanced our ongoing NOX-A12 plus radiotherapy trial in first-line
brain cancer patients,” said Aram Mangasarian, CEO of NOXXON. “In
addition, the balance sheet of the company has been significantly
strengthened and simplified, putting NOXXON in better negotiating
position with potential industrial and financial partners.”
Business Overview
NOXXON has been focused on clinical trials combining NOX-A12,
its anti-CXCL12 tumor microenvironment targeting agent, in two
distinct therapeutic combinations: 1) NOX-A12 plus immunotherapy
(anti-PD1 checkpoint inhibitors) and 2) NOX-A12 plus radiotherapy.
Each combination approach has a different underlying rationale and
mechanism of action, and thus diversifies the risk of NOXXON’s
clinical pipeline.
The combination approach of NOX-A12 plus standard of care
radiotherapy is currently being tested in a dose escalation Phase
1/2 trial in newly diagnosed patients with aggressive brain cancer
(glioblastoma) who would not benefit from standard of care
chemotherapy and whose tumor cannot be fully resected by surgery.
At multiple points in the trial, the independent Data Safety
Monitoring Board (DSMB) reviewed safety and tolerability of the
NOX-A12 combination and each time concluded that the trial should
continue as planned. All patients in the low dose cohort completed
six months of therapy in October 2020 and the data are very
encouraging. Tumor volume reductions were observed in two of three
patients during the six-month treatment, and in the third patient
in the period after a second surgery following continued NOX-A12
treatment. Maximum tumor volume reductions were 6% and 60% for the
first two patients. The third patient experienced 23% tumor volume
reduction relative to the post-second surgery baseline. All
patients in the mid dose cohort have been enrolled, with the first
patient completing four months of combination therapy and other
patients receiving their initial doses of NOX-A12 in October 2020.
This means that six months of therapy for Cohort 2 will complete in
April 2021.
NOXXON plans to advance the NOX-A12 plus radiotherapy
combination in first-line brain cancer if the ongoing Phase 1/2
data warrant additional studies. NOXXON believes that such a
pivotal trial following the current study could allow first filing
of a market approval application for NOX-A12 in 2024 with first
market approval targeted for 2025 if data are positive.
The Phase 1/2 trial studying the combination of NOX-A12 plus
immunotherapy in metastatic pancreatic and colorectal cancer
patients who had failed standard therapy reported final top-line
data in September 2020. Both the NOX-A12 mechanistic data as well
as the overall survival figures observed following treatment with
the combination of NOX-A12 and anti-PD1 have been highly
encouraging for the patient population treated in this study. The
patients enrolled in the trial all had advanced disease with liver
metastases and received on average their sixth-line of therapy in
colorectal cancer and their fourth-line of therapy in pancreatic
cancer. Despite the advanced disease and heavy pre-treatment,
overall survival at one year was 20%, assessed using the
Kaplan-Meier method. Notably, this group of longer-term survivors
included two pancreatic cancer patients who had received their
fourth-line of treatment.
NOXXON is planning to test the NOX-A12 plus immunotherapy
combination in second-line pancreatic cancer with a dosing regimen
of NOX-A12 optimized to induce anti-tumor immune responses. A
two-step approach is planned for this indication with a first trial
comparing two NOX-A12 chemotherapy combinations in second-line
patients followed by a pivotal trial comparing the best combination
to standard of care. With this approach, completion of the pivotal
trial and filing of the first market approval application for this
indication could be achieved in 2026 with approval targeted for
2027.
On the financing front, the company was able to raise €11.1
million net cash during the reporting period from a mix of private
placements, convertible bonds and warrant exercises, thereby
significantly strengthening its balance sheet.
NOXXON is closely monitoring the progress of COVID-19 and its
potential impact on its operations. As requested by the European
Medicines Agency (EMA), NOXXON has critically assessed the risks
and benefits of therapy continuation and inclusion of new trial
participants in its clinical trial of NOX-A12 combined with
radiotherapy in first-line brain cancer patients. Following a
thorough evaluation and discussion with the partners involved in
the trial, it has been decided to continue both the treatment of
enrolled patients and recruitment of additional patients. The
safety of patients, hospital staff and employees, as well as the
severity of the disease under study and the limited options
currently available for treatment, were important factors in this
decision. As there have been delays due to factors including
COVID-19, NOXXON has added further centers to the trial to ensure
adequate recruitment capacity to meet its targeted timelines.
Overall, the impact on trial recruitment, the organization and the
staff has been manageable.
The increased interest of investors in healthcare and the shift
in the types of investors considering financing small-cap European
biotech companies (particularly in France where over 150,000 new
investors opened equity investment accounts according to the French
regulator, the AMF), broadened the investor base of the capital
market and had a positive impact on NOXXON’s ability to raise
funds.
Business Highlights During First Half-Year of 2020
- Significant strengthening of balance sheet – NOXXON
raised €11.1 million net proceeds from multiple sources during the
first half of 2020, including €7.3 million via private placements.
The Dutch specialist fund Nyenburgh Investment Partners (NYIP) led
the largest of the private placements announced on May 8, 2020. In
addition, NOXXON has access to a remaining capacity of €16.2
million (nominal) from its convertible bonds financing with Atlas
after this financing agreement was amended in October 2020.
- Simplified capital structure – Increased price and
liquidity during the reporting period allowed the conversion of the
vast majority of outstanding warrants held by the investors Acuitas
and Yorkville at the beginning of the period.
- Timely advancement of NOX-A12 plus radiotherapy trial
despite COVID-19– Phase 1/2 clinical trial of NOX-A12 plus
radiotherapy in first-line brain cancer patients progressed well
despite COVID-19. On April 2, 2020 NOXXON announced completion of
patient recruitment for the first dose cohort in the Phase 1/2
brain cancer study of NOX-A12 plus radiotherapy. On April 24, 2020
the DSMB reviewed the available safety data from the low-dose group
and validated recruitment of patients in the mid-dose group of
NOX-A12. The recruitment of the first patient in the mid-dose group
was announced on June 30, 2020.
- More mature data from NOX-A12 plus immunotherapy trial
–overall survival data from the Phase 1/2 NOX-A12 and immunotherapy
combination trial in metastatic pancreatic and colorectal cancer
patients supports the benefit to patients from NOX-A12 plus
anti-PD-1 therapy. This data was presented by the principal
investigator of the trial, Dr. Niels Halama, Head of Department of
Translational Immunotherapy at the German Cancer Research Center
(DKFZ), Heidelberg and Medical Oncologist at the German National
Center for Tumor Diseases, at the American Association for Cancer
Research (AACR) Virtual Annual Meeting on April 27, 2020.
- New Supervisory Board Member – Oscar Izeboud joined the
Supervisory Board of NOXXON on June 30, 2020. Oscar brings both a
deep understanding of medicine and extensive experience in the
financing and business side of biotechnology. While leading life
science and healthcare investment banking at Kempen and NIBC, Oscar
successfully closed more than 100 transactions, including seventeen
IPOs and fifteen mergers or acquisitions. This experience combined
with his operational biotech background makes him a valuable asset
for NOXXON’s strategic development.
Business Highlights After June 30, 2020
- July 2020 – NOXXON announced that the first brain cancer
patient from the mid-dose cohort in the NOX-A12 plus radiotherapy
study reached four weeks of treatment and that the DSMB confirmed
safety and validated recruitment of additional patients.
- September 2020 – Dr. Niels Halama presented final
top-line clinical data from the Phase 1/2 NOX-A12 plus
immunotherapy combination trial in colorectal and pancreatic cancer
patients at the European Society for Medical Oncology (ESMO)
Virtual Congress 2020.
- October 2020 – NOXXON announced that two of the three
planned dose cohorts were fully recruited in the NOX-A12 plus
radiotherapy clinical trial.
First-half 2020 Financial Results (IFRS)
NOXXON Pharma did not generate any revenues in the first half of
2020 (H1 2020). The Group – NOXXON Pharma N.V. and NOXXON Pharma AG
– does not expect to generate any revenues from its product
candidates in development until the Group either signs a licensing
agreement or obtains regulatory approval and commercializes its
products or enters into collaborative agreements with third
parties.
Other operating income decreased to €33 thousand in H1 2020 (vs.
€274 thousand in H1 2019). Other services provided in 2020
generated lower other operating income than the sale of raw
materials and a partial waiver of management and Supervisory Board
members concerning their receivables from remuneration due from the
Group in H1 2019.
NOXXON dedicated its resources to research and development
(R&D) and general and administrative (G&A) expenses.
R&D expenses decreased to €942 thousand in H1 2020 (vs. €1,062
thousand in H1 2019). The decrease in R&D expenses was mainly
driven by lower costs for drug manufacturing, service fees and
other costs related to clinical trials and preclinical testing,
patent costs and consulting services, partly offset by higher
personnel expenses.
G&A expenses decreased to €988 thousand in H1 2020 (vs.
€1,238 thousand in H1 2019). The decrease in G&A expenses was
mainly driven by lower legal, consulting and audit fees, lower
public and investor relations and related expenses, as well as
lower other expenses, partly offset by higher personnel
expenses.
Foreign exchange losses increased to €7 thousand in H1 2020 (vs.
€2 thousand in H1 2019) as a result of increased volume of
purchases denominated in currencies other than Euro in H1 2020.
Finance cost increased from nil in H1 2019 to €4,173 thousand in
H1 2020. Finance cost in H1 2020 was predominantly due to the Atlas
convertible bonds financing with respect to the issuance and
conversion of convertible notes into equity and the recognition of
compound derivative financial instruments, the exercise of warrants
of the Yorkville equity line financing, the cashless exercise of
all remaining Acuitas warrants outstanding and fair value
adjustments of warrants outstanding.
Finance cost in H1 2020 was non-cash finance cost, except for
€105 thousand, thereof for transaction costs of €103 thousand borne
by the company in conjunction with the issuance of convertible
bonds.
Finance income (all non-cash) increased to €154 thousand in H1
2020 (vs. €75 thousand in H1 2019). The increase was due to the
derecognition gain of compound derivative financial instruments in
connection with the Atlas convertible bonds financing in H1
2020.
As a result of the above factors, the Group’s loss before income
tax increased to €5,923 thousand in H1 2020 (vs. €1,953 thousand in
H1 2019). The net cash used in operating activities amounted to
€1,811 thousand in H1 2020 vs. €2,687 thousand in H1 2019.
Consolidated Income Statements for the six months
ended
In € thousands
June 30, 2020
June 30, 2019
Other operating income
33
274
Research and development expenses
(942)
(1,062)
General and administrative expenses
(988)
(1,238)
Foreign exchange losses
(7)
(2)
Loss from operations
(1,904)
(2,028)
Finance cost
(4,173)
(0)
Finance income
154
75
Loss before income tax
(5,923)
(1,953)
Income tax
(0)
(1)
Net loss
(5,923)
(1,954)
Outlook
NOXXON is making progress in its ongoing Phase 1/2 trial of
NOX-A12 plus radiotherapy in first-line, inoperable brain cancer
(glioblastoma) patients who are shown by biomarker analysis of
their tumor tissue to be resistant to the current standard of care
chemotherapy. Currently, two of the three planned dose cohorts are
fully recruited. If study results are positive, NOXXON plans to
seek advice from authorities under its EU/US orphan drug
designation to confirm that its planned approach is acceptable to
complete development and achieve market approval in brain cancer.
NOXXON’s partnering goal for this combination is the identification
of industrial partners that will finance additional clinical trials
in brain cancer and other indications where radiotherapy is core to
the standard of care. NOXXON anticipates that at least partial
top-line clinical data including post-treatment follow-up from the
trial will be required to close a partnership in this area.
NOXXON published more mature data from the NOX-A12 clinical
trial in metastatic microsatellite stable pancreatic and colorectal
cancer patients in April 2020 and has published final top-line data
in September 2020. NOXXON believes that further clinical trials are
warranted based on this data, in particular in pancreatic cancer,
where it plans to focus its near-term efforts. The goal of NOXXON
is to find industrial partners that will not only provide anti-PD1
therapy but also financial support to conduct a trial.
To prepare for future trials leading to approval of NOX-A12,
NOXXON has made additional investment commitments for the
manufacturing of drug supply for clinical trials.
NOXXON’s long-term strategic plans now include the following
trials by indication:
NOX-A12 plus radiotherapy in Brain Cancer
- Completion of the ongoing Phase 1/2 dose escalation trial,
potentially with an expansion of the dose chosen for the pivotal
trial. Trial completion planned for 2021 (without any
expansion).
- Pivotal trial of NOX-A12 combined with radiotherapy in
first-line MGMT promoter unmethylated glioblastoma patients vs.
standard of care (assuming ongoing Phase 1/2 trial data supports
further development) planned initiation in 2022, with first market
authorization application targeted for 2024 and approval targeted
for 2025.
NOX-A12 plus immunotherapy in Pancreatic Cancer
- Two-arm Phase 2 “pick the winner” trial testing NOX-A12 plus
anti-PD1 antibody with two different standard of care chemotherapy
regimens to determine the choice of regimen for the pivotal trial.
Trial initiation planned for 2021 and completion in 2023.
- Pivotal trial of NOX-A12 combined with immunotherapy and
standard of care in second-line pancreas cancer vs. standard of
care, with market authorization application targeted for 2026 and
approval targeted for 2027.
The second clinical stage asset, NOX-E36, is also being prepared
for the next clinical trial. Manufacturing of clinical supply has
been contracted and is projected to be available in mid-2021.
Pre-clinical work comparing combination strategies for NOX-E36 in
solid tumors to identify the most promising approaches are also
advancing. NOXXON plans to initiate the first clinical trial of
NOX-E36 combinations testing safety in 2021.
NOXXON continues to evaluate other indications and therapeutic
combinations in which to test NOX‑A12 and NOX-E36 as well as the
relative priority of such indications for the overall corporate
strategy.
The Group will carefully monitor its available cash and
calibrate additional financings through various sources in order to
ensure its development plans and, to the extent deemed appropriate,
maintenance of a sufficient cash runway. Considering cash and cash
equivalents as well as financial assets as of June 30, 2020 of
€10.7 million and available, secured financing of €11.5 million
(nominal) as well as a subsequent amendment to this financing
agreement increasing its capacity by an additional €4.7 million
(nominal) drawable at the company’s discretion and subject to
customary conditions being met, cash reach of NOXXON will be into
Q1 2022, including the above planned manufacturing and clinical
trial commitments.
The Half-Year Financial Report 2020 can be downloaded from the
NOXXON website.
About NOXXON
NOXXON’s oncology-focused pipeline acts on the tumor
microenvironment (TME) and the cancer immunity cycle by breaking
the tumor protection barrier and blocking tumor repair. By
neutralizing chemokines in the tumor microenvironment, NOXXON’s
approach works in combination with other forms of treatment to
weaken tumor defenses against the immune system and enable greater
therapeutic impact. Building on extensive clinical experience and
safety data, the lead program NOX-A12 has delivered top-line data
from a Keytruda® combination trial in metastatic colorectal and
pancreatic cancer patients and further studies are being planned in
these indications. In September 2019 the company initiated an
additional trial with NOX-A12 in brain cancer in combination with
radiotherapy. The combination of NOX-A12 and radiotherapy has been
granted orphan drug status in the US and EU for the treatment of
certain brain cancers. The company’s second clinical-stage asset
NOX-E36 is a Phase 2 TME asset targeting the innate immune system.
NOXXON plans to test NOX‑E36 in patients with solid tumors both as
a monotherapy and in combination. Further information can be found
at: www.noxxon.com
Keytruda® is a registered trademark of Merck Sharp & Dohme
Corp
https://www.linkedin.com/company/noxxon-pharma-ag
https://twitter.com/noxxon_pharma
Disclaimer
Certain statements in this communication contain formulations or
terms referring to the future or future developments, as well as
negations of such formulations or terms, or similar terminology.
These are described as forward-looking statements. In addition, all
information in this communication regarding planned or future
results of business segments, financial indicators, developments of
the financial situation or other financial or statistical data
contains such forward-looking statements. The company cautions
prospective investors not to rely on such forward-looking
statements as certain prognoses of actual future events and
developments. The company is neither responsible nor liable for
updating such information, which only represents the state of
affairs on the day of publication.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20201029005198/en/
NOXXON Pharma N.V. Aram Mangasarian, Ph.D., Chief
Executive Officer Tel. +49 (0) 30 726247 0
amangasarian@noxxon.com
Trophic Communications Gretchen Schweitzer or Valeria
Fisher Tel. +49 (0) 172 861 8540 or +49 (0) 175 804 1816
noxxon@trophic.eu
NewCap Arthur Rouillé Tel. +33 (0) 1 44 71 00 15
arouille@newcap.fr